The calcium antagonists PY 108-068 and verapamil diminish the effects of angiotensin II: sites of interaction in the peripheral circulation of anaesthetized cats.

摘要

The sites of interaction between the vasoconstrictor angiotensin II (A II) and the calcium antagonists PY 108-068 (PY) (a dihydropyridine derivative) or verapamil (V) in different peripheral vascular beds were investigated using the microsphere method in chloralose-urethane anaesthetized open-chested cats. A II was infused intravenously into 27 cats at a rate of 0.15 microgram kg-1 min-1. Systemic haemodynamic variables and regional blood flow were measured immediately before and 10 min after the start of the infusion. While the infusion of A II continued, PY (3 micrograms kg-1 min-1), V (30 micrograms kg-1 min-1) or the vehicle was infused for 10 min into 9 cats each and the effects of this combined infusion were again measured at the end of the 10 min period. A II increased mean arterial blood pressure but decreased peripheral conductance and, to a smaller but still significant degree, cardiac output and peak acceleration of blood in the aorta (an ejection phase parameter of myocardial contractility). The calcium antagonists reversed these effects. Cardiac output and total peripheral conductance were increased even beyond the pre-A II level by PY. A II constricted the vascular beds of the kidney, small intestine, liver and skin. Arterio-venous shunt flow decreased. Vasoconstriction was also found in the stomach, spleen and in different parts of the heart with the exception of the subendocardial layer of the left ventricle, where blood flow increased and conductance remained unchanged. A II did not decrease conductance in different parts of the brain or in skeletal muscle. The vasoconstrictor effects of A II persisted or tended to be increased in most of the vascular beds of placebo treated animals. PY 108-068 and verapamil abolished the vasoconstrictor effects of A II in most of the vascular beds with the exception of the liver, the spleen, the skin and the arterio-venous shunts and caused vasodilatation in the heart. PY also induced vasodilatation in the brain and skeletal muscle, where A II had not induced vasoconstriction. The pattern of attenuation of A II effects was different from the pattern of vasodilatation induced by these and other calcium antagonists in the same cat preparation not treated with a vasoconstrictor. The sites of action of this dihydropyridine derivative (PY) on the peripheral circulation thus, appear to depend not only on the vascular bed but also on the presence of a vasoconstrictor influence at the time of investigation.