Positive chronotropic activity of angiotensin II in the pithed normotensive rat is primarily due to activation of cardiac beta 1-adrenoceptors.
In the pithed normotensive rat the intravenous administration of increasing doses of angiotensin II caused an increase in heart rate by a maximum of 93 +/- 6 beats/min. This increase in heart rate was diminished dose-dependently by the concomitant infusion of the angiotensin II analogue saralasin. It was not affected by acute bilateral adrenalectomy but strongly reduced by pretreatment with reserpine. By using the selective antagonists of alpha 1-, alpha 2-, beta 1- or beta 2-adrenoceptors prazosin, yohimbine, atenolol and ICI 118,551, respectively, it was shown that this tachycardia was mediated by stimulation of cardiac beta 1-adrenoceptors. Moreover, the high endogenous angiotensin II level following pithing contributed to the basal heart rate in the pithed rat model. From our experiments it may be concluded that angiotensin II induces tachycardia in the pithed rat primarily by stimulating the sympathetic ganglia leading to the release of noradrenaline, which subsequently activates cardiac beta 1-adrenoceptors.
Knape
J T
JT
Division of Pharmacotherapy, Faculty of Medicine, University of Amsterdam, The Netherlands.
van Zwieten
P A
PA
D000315:Adrenalectomy; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D003655:Decerebrate State; D006321:Heart / Q000294:innervation; D006339:Heart Rate / Q000187:drug effects*; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D009638:Norepinephrine / Q000378:metabolism / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D012504:Saralasin / Q000494:pharmacology
D011943:Receptors, Adrenergic, beta; D000804:Angiotensin II; D012504:Saralasin; D009638:Norepinephrine