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

To investigate the concentration-response relationship of angiotensin II with respect to its chronotropic effects, the sinus rate was recorded from canine isolated right atrial preparations perfused through the sinus node artery. 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 adrenergic neurons. The former response, but not the latter, was markedly reduced in preparations in which the right atrial ganglionated plexus was removed. Positive chronotropic responses were induced by angiotensin II over a wide range of concentrations (10(-12) - 5 x 10(6) M), with a maximum increment of 29.9 +/- 9.6 beats/min. Responses to low concentrations (angiotensin II, 10(-11) M) were monophasic and were abolished by propranolol. In contrast, the responses to higher concentrations (angiotensin II, 10(-6) M) were 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 being blocked by saralasin (nonselective angiotensin II antagonist). In conclusion, the data suggest that angiotensin II exerts its stimulant effects on the heart through receptors located either on cardiomyocytes or neurons, depending on the agonist concentration.