INTERACTION OF ATENOLOL WITH THE SYSTEMIC AND REGIONAL HEMODYNAMIC-EFFECTS OF HYDRALAZINE IN CONSCIOUS RENAL HYPERTENSIVE RABBITS

  • 1 January 1984
    • journal article
    • research article
    • Vol. 230  (1) , 205-213
Abstract
Using the radioactive microsphere technique, the interaction between atenolol and hydralazine was investigated 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-.mu.m micropheres distributed of 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. Atenolol interfered with the vasodilator response of hydralazine in the heart, skeletal muscles and the arteriovenous anastomoses. The .beta.-adrenoceptor anatagonist increased the endocardial/epicardial blood flow ratio and thereby abolished the negative effect of hydralazine on this parameter. The antihypertensive drugs acted synergistically only at a low hydralazine dose. A better hemodynamic profile was obtained after combined treatment as atenolol protected against the undesirable changes in regional myocardial blood flow distribution observed with hydralazine alone.