Cardiovascular Effects of Apamin and BRL 34915 in Rats and Rabbits

1. The cardiovascular effects of apamin, a selective blocker of certain calcium-activated potassium channels, and BRL 34915, a vasodilator thought to act by opening of potassium channels, have been investigated in vivo in rats and rabbits. 2. In anaesthetized normotensive rats, apamin (0.05 and 0.15 mg kg-1, i.v.) potentiated angiotensin II pressor responses but did not modify baseline blood pressure or heart rate. 3. Apamin (0.15 mg kg-1, i.v.) was without cardiovascular effects in rabbits. 4. BRL 34915 (0.1 and 0.3 mg kg-1, i.v.) lowered blood pressure in rats dose-dependently and caused reflex tachycardia. The heart rate increase was abolished by prior administration of the beta-adrenoceptor blocker bopindolol (0.1 mg kg-1, i.v.). 5. In anaesthetized rabbits, regional blood flow measurements (with radioactive tracer microspheres) showed that BRL 34915 (3 to 30 micrograms kg-1, i.v.) caused marked vasodilatation in the stomach, with increases in flow also to the heart and small intestine. Brain blood flow also tended to increase. Blood flow to the kidneys was reduced by BRL 34915, whereas flow to skeletal muscle was unchanged. 6. Apamin pretreatment did not modify the blood pressure lowering activity of BRL 34915 in rats. The site at which BRL 34915 acts to cause vasodilatation in vivo thus appears to be apamin-insensitive.