No major role for atrial natriuretic peptide in the vasodilator response to endothelin-1 in the spontaneously hypertensive rat.
Porcine endothelin-1 (endothelin) is a powerful releaser of atrial natriuretic peptide (ANP) from rat atrial myocytes in vitro. The fact that release is greater when atria are taken from spontaneously hypertensive rats (SHR) than normotensive control animals led to the suggestion that ANP release could be the basis of the prominent vasodilator responses seen in SHR in vivo. The present experiments were carried out in the anaesthetized, ganglion-blocked SHR to test this hypothesis. Bolus injections (1-4 nmol/kg) of ANP (atriopeptin III-rat) gave slowly developing (1-5 min), small (less than 10 mm Hg) falls in blood pressure associated with weak but consistent vasoconstrictor responses in the renal, mesenteric, carotid and hindquarters vascular beds. In contrast, i.v. injections of endothelin, 1 nmol/kg, induced rapid (less than 15 s), substantial (greater than 30 mm Hg) falls in blood pressure associated with vasodilation in the carotid and hindquarters vascular beds. In animals rendered essentially unresponsive to ANP following repeated i.v. injections of high doses (4-10 nmol/kg) of the peptide, endothelin still induced prominent vasodilator responses. Injections of endothelin given into the aortic arch in order to minimize contact with the atria, gave vasodepressor/vasodilator responses which were qualitatively similar and quantitatively somewhat greater than those following intra-jugular venous injection. Taken together these data suggest ANP release is not a major factor in the vasodilator effects of endothelin in the rat.
Fozard
J R
JR
Preclinical Research, Sandoz Pharma Ltd., Basel, Switzerland.
Part
M L
ML
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D016232:Endothelins; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D014664:Vasodilation / Q000187:drug effects*
D016232:Endothelins; D010455:Peptides; D009320:Atrial Natriuretic Factor