Rat amylin mediates a presser response in the anaesthetised rat: Implications for the association between hypertension and diabetes mellitus

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Abstract

Amylin (or islet amyloid polypeptide) has been reported to have binding sites in the central nervous system and the kidney and has been shown to activate plasma renin. It has been postulated that this peptide may 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 anaesthetised 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 novel amylin receptor antagonist AC413 (12 nmol·kg-1 min-1) reduced the presser response but not the hypotensive effects of amylin. The peptide antagonist calcitonin gene-related peptide (CGRP)8-37 12 nmol·kg-1·min-1) reduced the pressor response elicited by amylin and also antagonized the hypotensive effect of amylin. Pre-treatment of animals with the ganglion blocker mecamylamine (3 mg·kg--1 s.c.) reduced the pressor effect of amylin. Following the administration of the angiotensin converting enzyme inhibitor ramiprilat (300 nmol·kg-1 i.v.) the pressor response to amylin was reduced. Salmon calcitonin also elevated blood pressure in the anaesthetised rat; doses of amylin and salmon calcitonin associated with a pressor effect were associated with increases in plasma renin activity. We conclude that amylin may act centrally to elevate blood pressure in the anaesthetised rat, possibly through activation of the reni angiotensin system.

Original languageEnglish
Pages (from-to)256-261
Number of pages6
JournalDiabetologia
Volume40
Issue number3
DOIs
Publication statusPublished - 11 Mar 1997

Keywords

  • ACE in hibition
  • Amylin
  • Calcitonin
  • Calcitonin gene related peptide
  • Hypertension

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