Rat amylin mediates a pressor response in the anaesthetised rat: implications for the association between hypertension and diabetes mellitus.
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 pressor 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 pressor 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 renin angiotensin system.
Haynes
J M
JM
Department of Medicine, University of Melbourne, Victoria, Australia.
Hodgson
W C
WC
Cooper
M E
ME
D000595:Amino Acid Sequence; D000682:Amyloid / Q000494:pharmacology*; D000768:Anesthesia, General; D000803:Angiotensin I / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D003925:Diabetic Angiopathies / Q000503:physiopathology*; D005730:Ganglionic Blockers / Q000494:pharmacology; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D007022:Hypotension; D058228:Islet Amyloid Polypeptide; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D058287:Receptors, Islet Amyloid Polypeptide; D018000:Receptors, Peptide / Q000037:antagonists & inhibitors; D011993:Recombinant Fusion Proteins; D012474:Salmon
C106111:AC 413; D000682:Amyloid; D005730:Ganglionic Blockers; D058228:Islet Amyloid Polypeptide; D010446:Peptide Fragments; D010455:Peptides; D058287:Receptors, Islet Amyloid Polypeptide; D018000:Receptors, Peptide; D011993:Recombinant Fusion Proteins; C058636:calcitonin gene-related peptide (8-37); D008464:Mecamylamine; D002116:Calcitonin; D000803:Angiotensin I; D015740:Calcitonin Gene-Related Peptide