Interaction of atenolol with the systemic and regional hemodynamic effects of hydralazine in conscious renal hypertensive rabbits.
Using the radioactive microsphere technique, we investigated the interaction between atenolol and hydralazine after acute administration in conscious hypertensive rabbits. Hydralazine, 0.3 mg/kg i.v., increased heart rate, stroke volume and cardiac output and decreased total peripheral resistance. Only at higher doses (1.0 and 3.0 mg/kg i.v.) was a fall in arterial blood pressure observed due to a further reduction in total peripheral resistance. The drug caused vasodilatation in the heart, brain, kidneys, skeletal muscles, diaphragm, chest wall and large intestine and a, probably reflex-mediated, vasoconstriction in the skin, stomach and small intestine. In the heart hydralazine preferentially increased blood flow to the outer layers of the left ventricular wall, which resulted in a significant decrease in the endocardial/epicardial blood flow ratio. Hydralazine also greatly enhanced the percentage of 15-micron microspheres distributed to the lungs, indicating an increased arteriovenous anastomotic flow. Atenolol (1 mg/kg i.v.) elicited bradycardia and moderately reduced blood pressure due to a decrease in cardiac output. Pretreatment with atenolol attenuated the cardiac stimulation and thereby accentuated the hypotensive effect of hydralazine, 0.3 mg/kg. With the high hydralazine dose (3.0 mg/kg) the synergistic effect on blood pressure disappeared due to an increase in cardiac output, despite effective beta adrenoceptor blockade. Moreover, atenolol interfered with the vasodilator response of hydralazine in the heart, skeletal muscles and the arteriovenous anastomoses. The beta adrenoceptor antagonist increased the endocardial/epicardial blood flow ratio and thereby abolished the negative effect of hydralazine on this parameter. In conclusion, the antihypertensive drugs acted synergistically only at a low hydralazine dose.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001262:Atenolol / Q000494:pharmacology*; D001784:Blood Gas Analysis; D004347:Drug Interactions; D004553:Electric Conductivity; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006830:Hydralazine / Q000494:pharmacology*; D006977:Hypertension, Renal / Q000503:physiopathology*; D008297:Male; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects; D013318:Stroke Volume / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D006830:Hydralazine; D001262:Atenolol