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The Impact Of Aging On Potassium Channels Of Rat Small Artery Function And Gene Expression

Posted on:2010-10-19Degree:DoctorType:Dissertation
Country:ChinaCandidate:W X XueFull Text:PDF
GTID:1114360275961753Subject:Physiology
Abstract/Summary:PDF Full Text Request
BACKGROUND:Aging is a major risk factor of cardiovascular disease. During the process of aging, the vascular system undergoes a series of adaptations that lead to vascular disease. These changes not only include the formation of atherosclerotic plaques, but also involve changes of vascular activity. The mechanisms of changes of vascular activity are complicated, partly due to changes of ion channel. Some studies have shown that BKCa expression decreased, and NO synthesis reduced with age increasing, which affected the regulation of vasomotor function and the maintenance of normal hemodynamics. As a result, vasoconstriction increased. Potassium channels are the dominant ion conductive pathways in vascular muscle cells. Vascular smooth muscle cells express 4 different types of K+ channels, As such, their activity importantly contributes to determination and regulation of membrane potential and vascular tone. It has been suggested that the hyperpolarizing actions of the drugs cromakalim, pinacidil, nicorandil, and diazoxide are caused by the opening of K channels. 4-aminopyridine, the potassium channel blockers could contract vessel by inhibiting Kv channels. Our previous studies have proved that taurine enhances in IR rings but relaxes the contractions in normal rat aortic ring and TEA-sensitive K+ channel may be involved in both relaxation and contraction enhancement. Kv channels are the largest and most diverse class of ion channels. In all vascular smooth muscle cells described to date, voltage-dependent Kv currents are present, however, the biophysical characteristics vary depending on the vascular bed or segmental location along an arterial tree. It is therefore well conceived that the normal expression and function of Kv channels are prerequisites for the maintenance of the physiological contractile state of vascular SMCs. By the same token, altered Kv channel expression and function have been linked to many pathophysiological vascular conditions. Biophysical and pharmacological evidence suggests the existence of multiple components of Kv current within a single smooth muscle cell, including transient and delayed rectifier Kv currents. While studies have focused on the macroscopic current properties of the transient component, identifying the Kv channel genes that underlie these native currents has been difficult in blood vessels where protein determination is limited by the small amount of tissue. Using a combination of RT-PCR and Western blot analyses, we demonstrated that Kv1.2 and Kv1.5 were expressed in pulmonary arteries, cerebral arteries and mesenteric arteries, which suggest that Kv1.2 and Kv1.5 are important in the regulation of vascular contraction and relaxation.It is proved that the protein levels of BKCa were increased in old rat aorta compared with young rat. Electrophysiological experiments showed that BKCa current density was increased, and isolated experiments showed that the contraction of inhibiter of BKCa was increased; but Kv has no change in aging process in aorta. There was no change in pulmonary arteries and cerebral arteries of the old rats, but the protein levels of BKCa were diminished by about 50% in coronary arteries. The contraction of inhibiter of BKCa was also reduced in old rats coronary arteries. While the effect of the aging on the other types of potassium channels is not reported at present. To study the effect of K+ channel inhibiter on different vascular bed in aged rat is important to clarity the formation of cardiovascular disease in the elderly. Since aging and vascular and cardiac dysfunction seem to go hand in hand, it is a priority to identify the changes that are involved in age-induced changes and to unravel the mechanisms of these changes. This knowledge should help us understand these changes and potentially develop ways to decrease the effects of aging on the vasculature, preserve the quality of life, and alleviate cardiovascular disease in the growing older population.OBJECTIVE:(1) To investigate the effect of potassium channel blocker in rat cerebral artery, coronary artery, renal artery, pulmonary artery and mesenteric artery. Further, to study the effect of aging on the contraction of potassium channel blocker in different arteries. Potassium channel blockers include Tetraethtylamine (TEA), Glibenclamide (Gli), 4-aminopyridine (4-AP) and BaCl2 in the experiment.(2) On the basis of the result that the effect of potassium channel blockers on small arteries in adult rats and aged rats is different, we further explore the relationship between Kv channel function and gene expression of Kv1.2 and Kv1.5 to provide experimental basis for studying the occurrence of cardiovascular disease in the elderly.METHODS:1 The experimental method of vascular rings in vitroYoung or old rats were killed by cervical dislocation. The third-order branches of the superior mesenteric artery and renal arteries, and the second-order branches of the pulmonary artery, were isolated and cut into 2mm-long rings. Middle cerebral artery and coronary artery were isolated and cut into 2mm-long rings. The rings were mounted on a wire myograph (Multi Myograph System-610M, Danish Myo Technology A/S, Denmark) containing 5.0 ml of PSS (bubbled with 100% O2 and maintained at 37℃) for measurement of isometric tension. The rings were normalized according to standard procedures and stretched to a state equal to 100mmHg, 80mmHg, 80mmHg, 80mmHg, 80mmHg, respectively. A 2h equilibration period was allowed before any experimental intervention, and during equilibration, the bath was flushed every 20 minutes with the fresh PSS. After equilibration, the rings were activated 25 times with PSS containing 80 mmol/L KCl for 10 minutes. When the contraction induced by 80 mmol/L KCl was repeatable (the change was less than 10% between successive contractions), the concentration-response curves for BaCl2 (10-5, 3×10-5, 10-4, 3×10-4, 10-3, 3×10-3 and 10-2 mol/L),4-AP (10-5, 3×10-5, 10-4, 3×10-4, 10-3, 3×10-3 and 10-2 mol/L), Gli (10-5, 3×10-5, 10-4, 3×10-4, 10-3, 3×10-3 and 10-2 mol/L) and TEA (10-5, 3×10-5, 10-4, 3×10-4, 10-3, 3×10-3, 10-2 and 3×10-2 mol/L) were observed.2 The experimental method of RT-PCRYoung or old rats were killed by cervical dislocation, rat coronary, middle cerebral, renal, pulmonary, and mesenteric arteries were isolated and preserved in cold PSS solution. Total RNA was extracted with UNlQ-10 column total RNA extraction kit. After homogenization, the samples were processed according to the reagent instructions. The RNA was dissolved in diethyl pyrocarbonate–treated water and stored at -70°C. Optical density (OD) was measured to determine the RNA concentration (ratio of OD at 260 nm to OD at 280 nm >1.7). RT-PCR reaction were processed according to TaKaRa RNA PCR Kit (AMV) Ver. 3.0. The cDNA samples were amplified in an MJ Research (Waltham, MA) thermocycler. The number of PCR cycle for GAPDH was 29, for Kv1.2 was 30, for Kv1.5 was 35. The PCR products were electrophoresed through a 1.5% agarose gel (including 0.5μg/ml Ethidium Bromide), and amplified cDNA bands were visualized by Gel Dol 2000. The OD values in the channel signals were normalized to the OD values in the GAPDH signals; the ratios are expressed as % for semi-quantitative comparison.RESULTS:1. Effect of K+ channel inhibitor on cerebral artery, coronary artery, renal artery, pulmonary artery and mesenteric artery in young and aged rats.(1) Effect of 4-AP on middle cerebral artery, coronary artery, renal artery, pulmonary artery and mesenteric artery in young and aged rats.To investigate the effect of 4-AP (10-5, 3×10-5, 10-4, 3×10-4, 10-3, 3×10-3 and 10-2 mol/L) on middle cerebral artery in young rats and aged rats. We found the contraction of 4-AP in middle cerebral artery of young rats and aged rats. The contraction of 4-AP was more obvious in 10-3 mol / L, compared with in 10-5, 3×10-5, 10-4 and 3×10-4 mol / L. The contraction of 4-AP (10-3, 3×10-3 mol/L) in middle cerebral artery in old rats was decreased compared with young rats. The largest contraction amplitude of 4-AP was 4.38±0.43 mN in young rats, and its contraction rate was 187.54±34.96% and EC50 values were 6.18×10-4 mol/L; The largest contraction amplitude of 4-AP was 3.87±0.28 mN in old rats, and its contraction rate was 172.80±21.23% and EC50 values were 5.00×10-3 mol/L.To investigate the effect of 4-AP (10-5, 3×10-5, 10-4, 3×10-4, 10-3, 3×10-3 and 10-2 mol/L) on coronary artery in young rats and aged rats. We found the contraction of 4-AP in coronary artery of young rats and aged rats. The contraction of 4-AP was more obvious in 3×10-3 mol / L, compared with in 10-5, 3×10-5, 10-4, 3×10-4 and 10-3 mol / L. The contraction of 4-AP in coronary artery between young rats and aged rats has no significantly difference. The largest contraction amplitude of 4-AP was 9.29±0.91 mN in young rats, and its contraction rate was 151.61±34.10% and EC50 values were 2.54×10-3 mol/L; The largest contraction amplitude of 4-AP was 8.04±0.91 mN in old rats, and its contraction rate was 146.05±29.10% and EC50 values were 5.41×10-3 mol/L.To investigate the effect of 4-AP (10-5, 3×10-5, 10-4, 3×10-4, 10-3, 3×10-3 and 10-2 mol/L) on renal artery in young rats and aged rats. We found that the contraction of 4-AP in renal artery of young rats and aged rats. The contraction of 4-AP was more obvious in 3×10-3 mol / L, compared with in 10-5, 3×10-5, 10-4, 3×10-4 and 10-3 mol / L. The contraction of 4-AP in renal artery between young rats and aged rats has no significantly difference. The largest contraction amplitude of 4-AP was 7.61±0.47 mN in young rats, and its contraction rate was 167.73±19.02% and EC50 values were 1.65×10-3 mol/L; The largest contraction amplitude of 4-AP was 6.90±0.91 mN in old rats, and its contraction rate was 162.74±22.75% and EC50 values were 3.87×10-3 mol/L.To investigate the effect of 4-AP (10-5, 3×10-5, 10-4, 3×10-4, 10-3, 3×10-3 and 10-2 mol/L) on pulmonary artery in young rats and aged rats. We found the contraction of 4-AP in pulmonary artery of young rats and aged rats. The contraction of 4-AP was more obvious in 3×10-3 mol/L, compared with in 10-5, 3×10-5, 10-4, 3×10-4 and 10-3 mol/L. The contraction of 4-AP in pulmonary artery between young rats and aged rats has no significantly difference. The largest contraction amplitude of 4-AP was 3.49±0.27 mN in young rats, and its contraction rate was 67.83±5.39% and EC50 values were 1.06×10-3 mol/L; The largest contraction amplitude of 4-AP was 3.40±0.21 mN in old rats, and its contraction rate was 72.19±7.99% and EC50 values were 4.16×10-3 mol/L.To investigate the effect of 4-AP (10-5, 3×10-5, 10-4, 3×10-4, 10-3, 3×10-3 and 10-2 mol/L) on superior mesenteric artery in young rats and aged rats. We found the contraction of 4-AP in superior mesenteric artery of young rats and aged rats. The contraction of 4-AP was more obvious in 3×10-3 mol/L, compared with in 10-5, 3×10-5, 10-4, 3×10-4 and 10-3 mol/L. The contraction of 4-AP in superior mesenteric artery of young rats was increased compared with aged rats. The largest contraction amplitude of 4-AP was 11.58±1.29 mN in young rats, and its contraction rate was 144.34±18.02% and EC50 values were 4.16×10-3 mol/L; The largest contraction amplitude of 4-AP was 10.89±1.67 mN in old rats, and its contraction rate was 133.30±19.02% and EC50 values were 4.39×10-3 mol/L.(2) Effect of BaCl2 on middle cerebral artery, coronary artery, renal artery, pulmonary artery and mesenteric artery in young and aged rats.To investigate the effect of BaCl2 (10-5, 3×10-5, 10-4, 3×10-4, 10-3, 3×10-3 and 10-2 mol/L) on middle cerebral artery in young rats and aged rats. We found the contraction of BaCl2 in middle cerebral artery of young rats and aged rats. The contraction of BaCl2 was more obvious in 3×10-3 mol / L, compared with in 10-5, 3×10-5, 10-4, 3×10-4 and 10-3 mol / L. The contraction BaCl2 of middle cerebral artery between young rats and aged rats has no significantly difference. The largest contraction amplitude of BaCl2 was 2.99±0.38 mN in young rats, and its contraction rate was 130.92±31.92% and EC50 values were 2.68×10-3 mol / L; The largest contraction amplitude of BaCl2 was 3.87±0.16 mN in old rats, and its contraction rate was 132.80±21.23% and EC50 values were 3.21×10-3 mol/L.To investigate the effect of BaCl2 (10-5, 3×10-5, 10-4, 3×10-4, 10-3, 3×10-3 and 10-2 mol/L) on coronary artery in young rats and aged rats. We found the contraction of BaCl2 in coronary artery of young rats and aged rats. The contraction of BaCl2 was more obvious in 3×10-3 mol / L, compared with in 10-5, 3×10-5, 10-4, 3×10-4 and 10-3 mol / L. The contraction of BaCl2 in coronary artery between young rats and aged rats has no significantly difference. The largest contraction amplitude of BaCl2 was 9.44±1.01 mN in young rats, and its contraction rate was 187.90±24.67% and EC50 values were 2.01×10-3 mol/L; The largest contraction amplitude of BaCl2 was 9.30±0.47 mN in old rats, and its contraction rate was 166.05±29.10% and EC50 values were 2.60×10-3 mol/L.To investigate the effect of BaCl2 (10-5, 3×10-5, 10-4, 3×10-4, 10-3, 3×10-3 and 10-2 mol/L) on renal artery in young rats and aged rats. We found the contraction of BaCl2 in renal artery of young rats and aged rats. The contraction of BaCl2 was more obvious in 3×10-3 mol / L, compared with in 10-5, 3×10-5, 10-4, 3×10-4 and 10-3 mol / L. The contraction of BaCl2 in renal artery between young rats and aged rats has no significantly difference. The largest contraction amplitude of BaCl2 was 4.95±0.44 mN in young rats, and its contraction rate was 130.33±35.67% and EC50 values were 1.23×10-3 mol/L; The largest contraction amplitude of BaCl2 was 5.90±0.18 mN in old rats, and its contraction rate was 122.74±24.09% and EC50 values were 3.18×10-3 mol/L. To investigate the effect of BaCl2 (10-5, 3×10-5, 10-4, 3×10-4, 10-3, 3×10-3 and 10-2 mol/L) on pulmonary artery in young rats and aged rats. We found the contraction of BaCl2 in pulmonary artery of young rats and aged rats. The contraction of BaCl2 was more obvious in 10-3 mol/L, compared with in 10-5, 3×10-5, 10-4 and 3×10-4 mol/L. The contraction of BaCl2 in pulmonary artery between young and aged rats has no significantly difference. The largest contraction amplitude of BaCl2 was 4.93±0.42 mN in young rats, and its contraction rate was 115.32±9.22% and EC50 values were 2.79×10-3 mol/L; The largest contraction amplitude of BaCl2 was 5.24±0.95 mN in old rats, and its contraction rate was 106.01±13.77% and EC50 values were 9.22×10-4 mol/L.To investigate the effect of BaCl2 (10-5, 3×10-5, 10-4, 3×10-4, 10-3, 3×10-3 and 10-2 mol/L) on superior mesenteric artery in young rats and aged rats. We found the contraction of BaCl2 in superior mesenteric artery of young rats and aged rats. The contraction of BaCl2 was more obvious in 3×10-3 mol/L, compared with in 10-5, 3×10-5, 10-4, 3×10-4 and 10-3 mol/L. The contraction of BaCl2 in superior mesenteric artery of young rats was increased compared with aged rats. The largest contraction amplitude of BaCl2 was 8.03±0.85 mN in young rats, and its contraction rate was 98.93±4.72% and EC50 values were 3.45×10-3 mol/L; The largest contraction amplitude of BaCl2 was 7.89±0.01 mN in old rats, and its contraction rate was 113.49±13.58% and EC50 values were 4.92×10-3 mol/L.(3) Effect of TEA on middle cerebral artery, coronary artery, renal artery, pulmonary artery and mesenteric artery in young and aged rats.To investigate the effect of TEA (10-5, 3×10-5, 10-4, 3×10-4, 10-3, 3×10-3, 10-2 and 3×10-2 mol/L) on middle cerebral artery in young rats and aged rats. We found the contraction of TEA in middle cerebral artery of young rats and aged rats. The contraction of TEA was more obvious in 10-3 mol / L, compared with in 10-5, 3×10-5, 10-4 and 3×10-4 mol / L. The contraction of TEA in middle cerebral artery between young rats and aged rats has no significantly difference. The largest contraction amplitude of TEA was 0.84±0.06 mN in young rats, and its contraction rate was 37.11±7.61% and EC50 values were 2.68×10-3 mol / L; The largest contraction amplitude of TEA was 0.69±0.09 mN in old rats, and its contraction rate was 28.59±3.32% and EC50 values were 3.21×10-3 mol/L.To investigate the effect of TEA (10-5, 3×10-5, 10-4, 3×10-4, 10-3, 3×10-3, 10-2 and 3×10-2 mol/L) on coronary artery in young rats and aged rats. We found the contraction of TEA in coronary artery of young rats and aged rats. The contraction of TEA was more obvious in 10-2 mol / L, compared with in 10-5, 3×10-5, 10-4, 3×10-4, 10-3 and 3×10-3 mol/L. The contraction of TEA (10-2 and 3×10-2 mol/L) in coronary artery in old rats was decreased compared with young rats. The largest contraction amplitude of TEA was 7.01±0.82 mN in young rats, and its contraction rate was 131.97±67.86% and EC50 values were 7.67×10-2 mol/L; The largest contraction amplitude of TEA was 1.35±0.65 mN in old rats, and its contraction rate was 26.32±2.93% and EC50 values were 1.40×10-2 mol/L.To investigate the effect of TEA (10-5, 3×10-5, 10-4, 3×10-4, 10-3, 3×10-3, 10-2 and 3×10-2 mol/L) on renal artery in young rats and aged rats. We found the contraction of TEA in renal artery of young rats and aged rats. The contraction of TEA was more obvious in 3×10-2 mol / L, compared with in 10-5, 3×10-5, 10-4, 3×10-4, 10-3, 3×10-3 and 10-2 mol/L. The contraction of TEA in renal artery between young rats and aged rats has no significantly difference. The largest contraction amplitude of TEA was 2.04±0.43 mN in young rats, and its contraction rate was 45.24±3.65% and EC50 values were 1.07×10-2 mol/L; The largest contraction amplitude of TEA was 2.17±2.20 mN in old rats, and its contraction rate was 51.65±8.55% and EC50 values were 2.98×10-2 mol/L.To investigate the effect of TEA (10-5, 3×10-5, 10-4, 3×10-4, 10-3, 3×10-3, 10-2 and 3×10-2 mol/L) on pulmonary artery in young rats and aged rats. We found that the contraction of 4-AP in pulmonary artery of young rats and aged rats. The contraction of TEA was not obvious. The contraction of TEA in pulmonary artery between young rats and aged rats has no significantly difference. The largest contraction amplitude of TEA was 0.15±0.04 mN in young rats, and its contraction rate was 2.64±0.49 % and EC50 values were 1.09×10-2 mol/L; The largest contraction amplitude of TEA was 0.63±0.06 mN in old rats, and its contraction rate was 9.01±2.65 % and EC50 values were 1.40×10-2 mol/L.There was no effect of TEA (10-5, 3×10-5, 10-4, 3×10-4, 10-3, 3×10-3, 10-2 and 3×10-2 mol/L) in superior mesenteric artery of young rats and aged rats.(4) Effect of Gli on middle cerebral artery, coronary artery, renal artery, pulmonary artery and mesenteric artery in young and aged rats.There was no effect of Gli (10-5, 3×10-5, 10-4, 3×10-4, 10-3, 3×10-3 and 10-2 mol/L) in cerebral artery, coronary artery, renal artery, pulmonary artery and mesenteric artery of young rats and aged rats.2. The effects of aging on expression of Kv1.2 and Kv1.5 mRNA in rat small arteries.(1) The effects of aging on expression of Kv1.2 and Kv1.5 mRNA in rat blood vessel. Kv1.2 and Kv1.5 mRNA were all expressed in rat cerebral artery, coronary artery, renal artery, pulmonary artery and mesenteric artery.①The mRNA levels of Kv1.2 and Kv1.5 were increased in old rat cerebral artery compared with young rat.②The mRNA levels of Kv1.2 were enhanced in coronary artery, renal artery and pulmonary artery in old rat compared with young rat, but the mRNA levels of Kv1.5 have no significantly difference in coronary artery, renal artery and pulmonary artery between in old rat and young rat.③The mRNA levels of Kv1.2 have no significantly difference between in old rat mesenteric artery and in young rat, but the mRNA levels of Kv1.5 were decreased in old rat mesenteric artery compared with young rat. (2) The difference of vascular bed for the expression of Kv1.2 and Kv1.5 mRNA in young rat and old rat.①The mRNA levels of Kv1.2 among the arterial sites in young rat varied in the following order: coronary artery > cerebral artery > pulmonary artery > mesenteric artery > renal artery.②The mRNA levels of Kv1.2 among the arterial sites in old rat varied in the following order: cerebral artery > coronary artery > renal artery > pulmonary artery > mesenteric artery.③The mRNA levels of Kv1.5 among the arterial sites in young rat varied in the following order: cerebral artery > renal artery > coronary artery > mesenteric artery > pulmonary artery.④The mRNA levels of Kv1.5 among the arterial sites in old rat varied in the following order: cerebral artery > renal artery > coronary artery > pulmonary artery > mesenteric artery.CONCLUSION:1 Kv channel function and gene expression in old rats middle cerebral artery were changed compared with young rats. The contractive effect of 4-AP on middle cerebral artery in aged rats was significantly lower than young rats. In terms of gene expression, Kv1.2 and Kv1.5 mRNA expression in old rats middle cerebral artery are increased compared with young rats.2 In addition that the contractive effect of TEA on coronary artery in old rats was significantly lower than young rats, the effects of BaCl2 and glibenclamide on different small arteries in old rats and adult rats were no significant difference. BACKGROUND:Several studies have shown an association between essential hypertension, insulin resistance, and alterations in the circulating lipidic profile, which has been conventionally termed syndrome X. Insulin resistance, hyperinsulinemia, and mild hypertension have been induced in normotensive rats by chronic high-sucrose or high-fructose feeding. The precise mechanisms by which hypertension develops in fructose-fed rats have not yet been clearly defined. In addition, circulating catecholamines are elevated in sucrose-fed rats on a high salt diet, and it has been proposed that they contribute to hypertension through their vasoconstrictor. Since somatostatin administration inhibited the hypertension induced by fructose feeding, it has been proposed that the rise in BP observed in this model is secondary to the development of hyperinsulinemia. It has been demonstrated that vanadyl sulfate, a drug able to decrease insulin levels in nondiabetic rats, prevented fructose-induced hyperinsulinemia and hypertension in rats. Oral taurine may ameliorate fructose-induced hypertension in rats, but the effect of taurine on isolated aortic of IR rats has not been well documented.Taurine (taurine, TAU) is one of the most abundant amino acids in the plasma and cytosol. Besides its role in bile acid conjugation, taurine has been shown to be involved in numerous important physiological functions such as maintenance of the structural integrity of the membrane, regulation of calcium homeostasis, modulation of protein phosphorylation, osmoregulation, neuromodulation and neurotransmission. Frandoni et al reported that taurine exerted a powerful concentration-dependent, vasodilator action in rabbit isolated ear artery contracted with high potassium medium. Ristori et al reported that taurine was able to induce reduction of the basal contractile tone in rat aorta; taurine exerts a relaxing action in artery segments preconstricted with high potassium medium noradrenaline, and the effect of taurine is either independent of extracellular calcium, nor mediated by adrenoceptors. Although antidiabetic action of taurine was demonstrated in experimental animals, the effectiveness of taurine supplementation on human cases of insulin resistance is still not well studied. Anuradha et al reported that adding taurine to the diet of fructose-fed rats moderated the fructose-induced exaggerated glucose levels and hyperinsulinemia. Many studies show that taurine relaxes contracted arteries isolated from normotensive animals and hypertensive rats, but whether and how taurine affects vascular responses of IR rats to vasoactive agents has not been well documented. Present experiments were designed to study the effect of taurine on aortic rings isolated from normal and insulin resistance rat, and to explore its underlying mechanism(s), which should provide the experimental data to guide clinical application of antihypertensive drugs for patients with insulin resistance.OBJECTIVE:To observe and compare the effect of taurine on contractions of aortic rings isolated from normal (NC) and insulin resistance (IR) Sprague-Dawley rat, and to explore its underlying mechanism(s).METHODS:IR animal model was made by feeding rats with high fructose diet for 8 weeks. Aortic rings were isolated and suspended in tissue bath, and tensions were recorded isometrically. The effects of taurine on provoked contractions of the rings were assessed in absence or presence of one of well-know specific inhibitors.RESULTS:Taurine (20–80 mmol/L) concentration-dependently relaxed precontractions induced by KCl ( 30 mmol/L) and phenylephrine (1μmol/L) in NC rings, but enhanced the precontractions in IR rings. Denudation of the endothelium and pretreatment with NG-nitro-L-arginine methylester ester (0.1 mmol/L) reversed the contraction enhancement of taurine to relaxation in IR rings. Tetraethylammonium (10 mmol/L) nearly abolished taurine-induced relaxation of NC rings, and augment taurine-induced contraction enhancement in IR rings. Iberiotoxin (100 nmol/L) only augmented the contraction enhancement in IR rings. 4-aminopyridine (1 mmol/L), glibenclamide (10μmol/L) and indomethacin (10μmol/L) had no influence on the effect of taurine in both NC and IR rings.CONCLUSION:Taurine enhances in IR rings but relaxes the contractions in normal rat aortic ring; the enhancement is endothelium-dependent and the relaxation is endothelium-independent. TEA-sensitive K+ channel may be involved in both relaxation and contraction enhancement; BKCa channel dysfunction and endothelium-derived substances may be related to the contraction enhancement induced by taurine in IR aorta.
Keywords/Search Tags:potassium channels, voltage-dependent K+ channels, aging, small arteries, gene expression, taurine, insulin resistance, thoracic aorta, potassium channel, vascular endothelial
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