Concentration-dependent effects of angiotensin II on sinus rate in canine isolated right atrial preparations

To investigate the concentration-response relationship of angiotensin II wi th respect to its chronotropic effects, the sinus rate was recorded from ca nine isolated right atrial preparations perfused through the sinus node art ery. Nicotine (5 x 10(-5) M) injection induced an early, atropine-sensitive bradycardic response and a more delayed propranolol-sensitive tachycardic response, suggesting that the preparations contained both cholinergic and a drenergic neurons. The former response, but not the latter, was markedly re duced in preparations in which the right atrial ganglionated plexus was rem oved. Positive chronotropic responses were induced by angiotensin II over a wide range of concentrations (10(-12) - 5 x 10(6) M), with a maximum incre ment of 29.9 +/- 9.6 beats/min. Responses to low concentrations (angiotensi n II, 10(-11) M) were monophasic and were abolished by propranolol. In cont rast, the responses to higher concentrations (angiotensin II, 10(-6) M) wer e not abolished by propranolol and were biphasic (early response, 29.9 +/- 12.1 beats/min; later response, 18.6 +/- 9.0 beats/min), the early response being blocked by losartan (AT(1) antagonist) but not the later one, both b eing blocked by saralasin (nonselective angiotensin II antagonist). In conc lusion, the data suggest that angiotensin II exerts its stimulant effects o n the heart through receptors located either on cardiomyocytes or neurons, depending on the agonist concentration.