Autonomic nervous system‐dependent and ‐independent cardiovascular effects of exendin‐4 infusion in conscious rats

摘要: Background and purpose: Glucagon-like peptide-1 (GLP) receptor agonists are promising therapeutic agents for the treatment of type II diabetes, but effects other than those on glucoregulation need assessing. Cardiovascular actions bolus doses GLP agonist exendin-4 have been reported, to date continuous infusions not described. Experimental approach: The regional haemodynamic possible underlying mechanisms 6 h were measured in conscious, chronically instrumented rats. Key results: A infusion (up 6 pmol kg−1 min−1) only modestly influenced blood pressure, caused substantial, opposing, regionally selective vascular tachycardia. major involvement β-adrenoceptors vasodilator cardiac was identified, with little or no direct contribution from α-adrenoceptors vasoconstriction seen. Under conditions where α- antagonized, when ganglionic transmission blocked, a marked vasoconstrictor effect revealed mesenteric hindquarters beds (about 50% fall conductances). No role endogenous angiotensin II, vasopressin, endothelin, neuropeptide Y prostanoids could be shown these exendin-4. Conclusions implications: results show an important autonomic nervous system cardiovascular also non-autonomically mediated action, mechanism which remains identified.