RAT AMYLIN MEDIATES A PRESSOR-RESPONSE IN THE ANESTHETIZED RAT - IMPLICATIONS FOR THE ASSOCIATION BETWEEN HYPERTENSION AND DIABETES-MELLITUS

Amylin (or islet amyloid polypeptide) has been reported to have bindin g sites in the central nervous system and the kidney and has been show n to activate plasma renin. It has been postulated that this peptide m ay be an important mechanistic link between hypertension and diabetes in the insulin resistance syndrome. To explore this issue, the effects of rat amylin on mean arterial blood pressure were investigated in an aesthetised rats. Amylin elicited a presser response of approximately 10 mmHg (maximal at 100 pmol . kg(-1)) which was apparent within 30-60 s and persisted over 15 min. At higher concentrations amylin elicited a hypotensive response (negative log IC50 8.52 mol . kg(-1)). The nov el amylin receptor antagonist AC413 (12 nmol kg(-1) . min(-1)) reduced the presser response but not the hypotensive effects of amylin. The p eptide antagonist calcitonin gene-related peptide (CGRP)(8-37) (12 nmo l . kg(-1) . min(-1)) reduced the presser response elicited by amylin and also antagonized the hypotensive effect of amylin. Pre-treatment o f animals with the ganglion blocker mecamylamine (3 mg . kg(-1) s.c.) reduced the presser effect of amylin. Following the administration of the angiotensin converting enzyme inhibitor ramiprilat (300 nmol . kg( -1) i.v.) the presser response to amylin was reduced. Salmon calcitoni n also elevated blood pressure in the anaesthetised rat; doses of amyl in and salmon calcitonin associated with a presser effect were associa ted with increases in plasma renin activity. We conclude that amylin m ay act centrally to elevate blood pressure in the anaesthetised rat, p ossibly through activation of the renin angiotensin system.