Angiotensin (ATN) and ergonovine (ERG) are known to cause vasoconstriction of the coronary bed. However, ATN effects have been described mainly on the coronary resistance vessels, while ERG effects have been described on proximal conductance vessels. Recent studies have shown that proximal and distal coronary arteries are regulated independently. To examine both proximal and distal effects of ATN and ERG on the same heart, we studied 7 intact dogs, anesthetized with Innovar (Fentanyl 0.4 mg, Droperidol 20 mg, in 1 ml) and nitrous oxide, which were subjected to direct left anterior (LAD) coronary infusion of angiotensin (0.1, 0.5 and 5 micrograms/min) and ergonovine (0.5, 5, and 25 micrograms/min). Using a quantitative angiographic technique to measure artery dimensions and microspheres to measure flow, ERG infusion showed significant large artery constriction at all doses (maximum: 38.9 +/- 7.8% area reduction), and a significant decrease in LAD coronary artery flow, while endocardial/epicardial flow ratio remained unchanged. ATN produced a biphasic effect on the large coronary arteries. The lowest dose produced constriction (12.3 +/- 3.7% area reduction), which returned toward control value with the 0.5 micrograms/min dose (6.0 +/- 1.0% area reduction), and the 5 micrograms/min dose (1.5 +/- 9.5% area reduction), and no significant changes were observed in LAD flow with ATN infusion. Endocardial/epicardial ratio was unchanged, but aortic pressure was significantly increased during 0.5 and 5 micrograms/min ATN infusion. Coronary resistance (pressure/flow) increased with both ERG and ATN. ERG and ATN produce large and small coronary artery constriction. The coronary response to ERG in dogs is similar to the human coronary response, even though previous data indicated a minimal constrictor response to ERG in canine coronary arteries.

The effects of the converting enzyme inhibitor (SQ 20881) on the pulmonary circulation were investigated in 13 patients in whom systemic hypertension developed following coronary artery bypass surgery. Pulmonary vascular resistance was decreased by the inhibitor, from 128 +/¿ 19 to 92 +/- 20 dynes sec cm-5 (or by 30 +/- 7 per cent; P less than 0.005), and this resulted in a decrease in mean pulmonary artery pressure from 17 +/- 1 to 13 +/- 1 mm Hg (or by 23 +/- 3 per cent, P less than 0.005). Consequently, right ventricular work was decreased by the inhibitor by 30 per cent (P less than 0.01), despite an increase in cardiac output (increase in stroke volume) by 16 +/- 6 per cent (P less than 01). This increase occurred despite a 13 +/- 3 per cent decrease in right ventricular filling pressure. The changes in pulmonary vascular resistance correlated with the pretreatment plasma renin activity (r = 0.74, P less than 0.01), as did the decrease in mean pulmonary artery pressure (R = 0.82, P less than 0.001), but neither change was related to the decrease in left ventricular fillling pressure nor to changes in cardiac output or mean arterial pressure. These results indicate that blockade of the formation of angiotensin II by the converting enzyme inhibitor results in reductions in pulmonary vascular resistance and pulmonary artery pressure which are unrelated to alterations in left ventricular function. Thus, angiotensin inhibition may have therapeutic value in various clinical states characterized by pulmonary hypertension--especially if renin levels are high.

The role of the renin-angiotensin system in the regulation of the systemic and coronary circulations during sodium depletion was studied in conscious normotensive dogs by i.v. administration of teprotide (0.5 mg/kg), an angiotensin-converting enzyme inhibitor, and saralasin (0.05-5 mug/kg per min), an angiotensin-receptor antagonist. Sodium depletion was produced by administering a low sodium diet and furosemide for 5 days. Administration of both teprotide and saralasin lowered systemic arterial blood pressure and total peripheral vascular resistance. Simultaneously, cardiac output increased, but left ventricular end-diastolic pressure, dP/dt, and dP/dt/P did not change significantly. Furthermore, both agents reduced diastolic coronary vascular resistance and increased coronary blood flow, but did not affect myocardial oxygen consumption, left ventricular work, or myocardial efficiency. These systemic and coronary vasodilator effects of teprotide and saralasin, however, were not observed in normal dogs on a regular sodium diet; in this group, the only effect noted was a slight increase in arterial pressure during saralasin infusion. Arterial plasma concentration of norepinephrine did not differ between normal and sodiumdepleted dogs, nor did it change significantly after teprotide administration. These results suggest that, during salt depletion, angiotensin II exerts an active vasoconstrictor action on the systemic and coronary vessels, but has no significant effects on myocardial contractility or energetics. It also appears likely that the increase in cardiac output observed in sodiumdepleted dogs after angiotensin inhibition was caused, at least in part, by the decrease in systemic arterial pressure.