Antagonistic Effect of Human α-Calcitonin Gene–Related Peptide (8–37) on Regional Hemodynamic Actions of Rat Islet Amyloid Polypeptide in Conscious Long-Evans Rats

Rat synthetic amidated islet amyloid polypeptide (IAPP) was infused into conscious Long-Evans rats chronically instrumented for the measurement of regional hemodynamics. Rat IAPP (0.25–2.5 nmol · kg⁻¹ · min⁻¹) had dose-dependent tachycardiac and hypotensive effects. Renal blood flow increased at all dose levels in association with incremental rises in renal vascular conductances. Hindquarters blood flow and vascular conductance increased at the higher dose levels, but mesenteric blood flow fell with mean arterial blood pressure (i.e., there was no change in mesenteric vascular conductance). Concurrent infusion of 25 nmol · kg⁻¹ · min⁻¹ human α-calcitonin gene–related peptide (CGRP) (8–37) abolished the hypotensive, tachycardiac, and renal and hindquarters vasodilator effects of rat IAPP, and during administration of both peptides, there was a transient renal and sustained mesenteric vasoconstriction. When the infusion of human α-CGRP (8–37) was stopped, the effects of the continued infusion of rat IAPP were reestablished. The results indicate that the reported ability of IAPP to induce insulin resistance cannot be due to decreased skeletal muscle blood flow. In addition, human α-CGRP (8–37) is an effective antagonist of the hemodynamic actions of rat IAPP. Because it has been shown previously that human α-CGRP (8–37) antagonizes the hemodynamic effects of human α-CGRP, these results, collectively, indicate that human α-CGRP and rat IAPP might act on the same receptor at which human α-CGRP (8–37) is an effective antagonist or that the latter is a nonselective antagonist of separate receptors on which human α-CGRP and rat IAPP act.