Modification of the vasoconstrictor effects of noradrenaline and serotonin by the selective calcium antagonist PY 108-068 in the peripheral circulation of anesthetized cats.

The effects of a noradrenaline (NA, 1 microgram/kg min) or serotonin (5-HT, 10 micrograms/kg min) infusion on regional blood flow and conductance were assessed with tracer microspheres before and after administration of the calcium-antagonist PY 108-068 (PY; 30 micrograms/kg). Chloralose-urethane-anesthetized cats were pretreated with propranolol 1 mg/kg i.v. or chlorisondamine 1 mg/kg i.v. for the experiments with NA or 5-HT, respectively. PY attenuated the NA-induced increase of blood pressure and the decrease of total peripheral conductance. The NA-induced vasoconstriction, occurring mainly in the kidneys, adrenals, liver, spleen, and arteriovenous shunts, was significantly attenuated by PY. The vessels of heart, stomach, pancreas, and skeletal muscle were not constricted by NA. In contrast, 5-HT dilated or tended to dilate almost all vascular beds examined. Only arteriovenous shunts were constricted. PY did not antagonize this vasoconstrictor effect. Moreover, after but not before PY treatment, a coronary vasoconstrictor effect of 5-HT was seen. Antivasoconstrictor effects of PY were observed both in organs where dihydropyridines normally elicit vasodilatation and in organs where such compounds have no vasodilator effects in the absence of a vasoconstrictor infusion. The regional distribution of the antivasoconstrictor effects was different for each vasoconstrictor tested so far (angiotensin II, 5-HT, and NA). The sites of action of calcium antagonists in peripheral blood vessels appear to depend on the mechanism of activation operating at that site and at the time of the investigation.