| Background: UrotensinⅡ(UⅡ) is an 11-amino acid vasoactive cyclic peptide originally isolated from the goby fish spinal cord. UⅡhas been found in a wide range, not only in cardiovascular system, endocrine system, but also in central nervous system from fishes, rats to human. G-protein coupled orphan receptor (GPR14) is a specific receptor of UⅡ. UⅡis the most potent mammalian vasoconstrictor identified so far which greater than endothelin-1. UⅡevoked differential responses depending on the kinds of species and vessels. UⅡmay act as a neurotransmitter and/or neuromodulator in the central nervous system. Intracerebroventricular (ICV) injection of UⅡprovoked various behavioral, cardiovascular, motor and endocrine responses in rats. In conscious sheep, ICV infusion of UⅡcaused large increases in heart rate (HR) and cardiac contractility. In normotensive and hypertensive conscious rats, ICV administration of UⅡsignificantly increased mean arterial pressure (MAP) and HR, and greater responses had been found in hypertensive rats. In the anesthetized rats, microinjection of UⅡinto specific areas of brain, the paraventricular nucleus (PVN) of the hypothalamus and the arcuate nucleus, significantly increased MAP and HR while microinjection of UⅡinto the A1 area induced dose-related and long-lasting hypotensive and bradycardiac responses. Thus, central UⅡmay play different cardiovascular roles in different brain areas and different neurons.Our previous study had shown that UⅡinhibited the carotid sinus baroreflex. UⅡdecreased neuronal activity by potentiating GABA receptor-mediated Cl- current in hippocampal CA1 neurons and PVN neurons. However, the exact sites and mechanisms of UⅡtaking action have not been demonstrated clearly yet. As we all known, rostral ventrolateral medulla (RVLM) is a critical central region in the regulation of sympathetic outflow and plays an important role in the baroreflex. The activities of neurons in RVLM can determin peripheral vascular tone and arterial blood pressure. Therefore, RVLM may be an important possible link in the pathogenesis of hypertension, and in turn acts as a possible therapeutic target too.In the present study, we investigated the effects of UⅡon BP, HR and RSNA in anesthetized rats through the method of microinjection UⅡinto RVLM, and furthermore attempted to elucidate the mechanisms involved.Aim: To study the effects of UⅡmicroinjected into RVLM neurons on blood pressure (BP), heart rate (HR) and renal sympathetic nerve activity (RSNA) in anesthetized rats. Methods: BP, HR and RSNA were simultaneously recorded after microinjecting of drugs into RVLM.Results: (1) After 200nl UⅡ0.3, 3 and 30nmol/L microinjected into RVLM, BP, HR and RSNA were increased significantly. The pressor responses began within 10~15 min and reached its peak in 30~40 min. The peak pressor responses (MAP) of UⅡ0.3nmol/L, 3nmol/L and 30nmol/L were from 86.12±4.66mmHg to 99.42±3.85mmHg (p<0.01), 86.67±4.41mmHg to 98.92±4.20mmHg (p<0.01) and 86.65±6.39mmHg to 101.89±6.34 mmHg (p<0.01). HR was increased from 322.80±9.37bpm to 342.60±7.97bpm (p<0.05), 325.33±5.27bpm to 351.50±7.53bpm (p<0.05) and 311.00±10.96bpm to 338.33±11.56bpm (p<0.01). RSNA was increased by microinjection of UⅡ0.3nmol/L, 3nmol/L and 30nmol/L to 141.93±6.74% (p<0.01), 133.96±6.88% (p<0.01) and 142.78±9.94% (p<0.01). (2) Pretreatment with BIM23127 (a potent antagonist of UⅡreceptor GPR14) 300nmol/L, 200nl significantly suppressed the effects of UⅡ. (3) Pretreatment withω-conotoxin GVIA (an inhibitor of N-type calcium channel) 200nmol/L, 200nl significantly suppressed the effects of UⅡ. (4) Pretreatment with PD98059 (an inhibitor of MAPK kinase) 25μmol/L, 200nl attenuated the increase response induced by the microinjection of UⅡ.Conclusion: The present study for the first time demonstrated that the microinjection of UⅡinto RVLM increased BP, HR and RSNA significantly in rats, which mediated by the UⅡ receptor GPR14, N-type calcium channel and MAPK pathway. |
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