| Arterial baroreceptors are mechanosensitive nerve endings that innervate adventitia of carotid sinuses and aortic arch. Changes in arterial blood pressure are sensed indirectly through the baroreceptors' responsiveness to mechanical deformation during vascular stretch. Changes in the frequency of baroreceptor afferent discharge transmitted to the central nervous system trigger reflex adjustments that buffer or oppose the change in pressure; that is, the baroreceptor reflex provides a powerful negative feedback mechanism of blood pressure regulation. Many studies have shown there are mechanosensitive ion channels in baroreceptors, many drugs may act on the channels leading to modulation of baroreceptor activity.Cholecystokinin is widely distributed in the central and peripheral nervous systems. A considerable body of evidence indicates that CCK-8 exerts its effects via two distinct subtypes of receptors, CCK-AR and CCK-BR. Many studies showed that cholecystokinin octapeptide (CCK-8), the active fragment of endogenous CCK, had cardiovascular actions in both conscious and anesthetized animals, and elicited dose-dependent increase in arterial blood pressure and a variable change in heart rate. To exclude the effect of the central nervous system, Gaw et al reported that injection of CCK-8 caused a dose-dependent increase in arterial blood pressure and a bradycardia in pithed rats, and the above effects of CCK-8 were inhibited by administration of CCK-AR antagonists, loxiglumide and devazepide, while not by treatment with CCK-BR antagonist, L-365, 260. However, there are little reports on whether CCK-8 affects carotid sinus baroreflex which is of the most importance to the regulation of cardiovascular. So, the present work was undertaken to study the effects of CCK-8 on carotid sinus baroreflex and baroreceptor activity in anesthetized male rats with isolated carotid sinus perfusion in vivo. 1 Cholecystokinin octapeptide inhibits carotid sinus baroreflex in anesthetized ratsCCK-8 is an active functional fragment of CCK. It has been established that CCK-8 can alter cardiovascular functions on conscious or anesthetized animals. The purpose of this study was to determine the effect of cholecystokinin octapeptide (CCK-8) on carotid sinus baroreflex in 36 anesthetized male rats by isolated carotid sinus perfusion in vivo. The results obtained are as follows. (1) parameters of carotid sinus baroreflex are as follows: peak slope (PS) 0.47±0.01, reflex decrease(RD) is 47.67±3.21, threshold pressure(TP)is 65.42±1.82, saturation pressure(SP)is 168.87±1.58; (2) By perfusion with CCK-8 (0.1 μmol/L), the functional curve of baroreflex was shifted to the right and upward, PS was decreased to 0.35±0.02 and RD was decreased to 36.50±2.76(P<0.001), while TP and SP were significantly increased to 72.36±2.94 and 178.49±2.86; By perfusion with CCK-8 (0.5 μmol/L), the functional curve of baroreflex was further shifted to the right and upward, PS and RD were decreased to 0.3±0.01(P<0.001)and 31.17±1.14(P<0.001), TP and SP were increased to 75.84±1.56 (P<0.001)and 183.79±3.19(P<0.001); By perfusion with CCK-8 (1.0 μmol/L), the functional curve of baroreflex was shifted to the right and upward further comparing to group CCK-8 (0.5 μmol/L), PS and RD were decreased to 0.21±0.01(P<0.001)and 22.10±2.68(P<0.001), while TP and SP were increased to 82.04±2.24(P<0.01)and 199.01±2.43(P<0.001); Among the functional parameters of carotide baroreflex, the changes in RD, PS and TP were dose-dependent. (2) Pretreatment with proglumide (100 μmol/L), a nonselective CCK receptor antagonist, the inhibitory effect of CCK-8 (0.5 μmol/L) on the baroreflex was significantly attenuated. PS and RD were increased to 0.41±0.02(P<0.001)and 43.67±1.95(P<0.001); TP and SP were decreased to 71.19±1.47(P<0.05) and 177.32±2.47(P<0.05). (3) Pretreatment with L-NAME (100 μmol/L), an inhibitor of NO synthase, did not affect the inhibitory effect of CCK-8 (0.5 μmol/L); (4) Preperfusion with B...
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