The injection of angiotensin 11, 1.0 mcg./Kg., into pentobarbital anesthetized dogs produced a significant increase in systolic and diastolic blood pressures and myocardial blood flow, a slight increase in the force of right ventricular contraction, and no significant effects on heart rate. Cardiac output was initially decreased; but within 80 to 100 seconds after angiotensin I1 administration, a secondary rise was noted. The rise in diastolic pressure was significantly greater than that of the systolic pressure at the 5 per cent level. The coronary flow increase appeared to be dependent entirely o n the increase in diastolic blood pressure. I n coronary perfusion studies, angiotensin I1 produced myocardial vasoconstriction when injected either intravenously or intra-arterially. These effects were mediated by both direct musculotropic actions and the sympathetic nervous system since acute sympathectomy reduced, but did not abolish, the activity of angiotensin 11. T h e sympathetic component of the cardiovascular effects of angiotensin I1 appear to be via the alpha receptors since nethalide markedly otentiated the activity of angiotensin 11. T h e effect of pretreatment with phenoxytenzamine, atropine, or dichloroisoproterenol on the cardiovascular responses to angiotensin I1 was also evaluated.
HERE HAVE BEEN several conflicting reports Tconcerning
the effects of angiotensin I1 on coronary blood flow. Investigators have reported that angiotensin decreases coronary blood flow ( I ) , produces coronary vasoconstriction (2, R), produces a transient reduction in coronary flow followed by a transient increase in flow (4), increases coronary vascular resistance without altering coronary flow (5), produces no alteration in coronary flow (e), and produces an increase in coronary blood flow (7). This paper reports a group of studies designed to facilitate a better understanding of certain cardiovascular actions of angiotensin 11.
EXPERIMENTAL
Mongrel dogs of either sex, weighing between 10.2 and 18.6 Kg., were anesthetized by an intra-venou5 injection of pentobarbital sodium (35 mg./ Kg.) and the trachea cannulated. Femoral arterial blood pressure was recorded with a Statham pressure transducer (model P23AC) following cannulation of the right femoral artery. Heart rate was determined from the blood pressure tracing.
Cardiac output flow measurements were performed utilizing an electromagnetic flowmeter (Medicon FM-6). described by Olmsted (8). The animals were placed on artificial respiration with a Harvard respirator (model 606) utilizing a mixture of 95% 0 2 and 5% CO?. The thoracic cavity was entered a t the fourth intercostal space using electrocautery to minimize bleeding. The lungs were retracted and the pericardiuin incised and secured to the chest wall with wound clips to create a pericardial sac whereby