CALCIUM CHELATION AND CALCIUM-CHANNEL BLOCKADE IN ANESTHETIZED ACUTE RENOVASCULAR HYPERTENSIVE DOGS

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  • 1 January 1984
    • journal article
    • research article
    • Vol. 10  (6) , 366-370
Abstract
Acute animal studies were conducted to explore the effect of Ca manipulation on blood pressure and in the blood pressure response to angiotensin blockade under conditions of renovascular hypertension in anesthetized mongrel dogs. Ethylenediaminetetraacetic acid (EDTA) was used to lower serum Ca (SCa) levels, while nifedipine was infused i.v. to antagonize Ca at the cellular level. Angiotensin blockade was accomplished by infusion of the competitive inhibitor of angiotensin. saralasin. Following renal artery clamping, mean arterial pressure (MAP) increased a mean of 21 .+-. 3 mm Hg from 116 .+-. 5-137 .+-. 6 mm Hg (P < 0.001) in 23 studies. Lowering of SCa by 30 min of EDTA infusion in 9 of these animals resulted in a mean fall of -21 .+-. 4 mm Hg from 127 .+-. 7 to 105 .+-. 7 mm Hg (P < 0.005). A 30 min infusion of nifedipine solution in 5 animals did not significantly affect blood pressure. In 9 normocalcemic hypertensive animals, saralasin reduced MAP from 138 .+-. 8 to 127 .+-. 8 mm HG (P < 0.001). In 9 animals with lowered SCa (6.9 .+-. 0.2 mg/dl) due to 30 min of EDTA infusion, the same dose of saralasin resulted in a greater reduction of MAP from 127 .+-. 7 to 78 .+-. 9 mm Hg (P < 0.001). Nifedipine and saralasin used together in 5 hypertensive animals resulted in the reduction of MAP from 155 .+-. 14 to 131 .+-. 14 mm Hg (P < 0.01). When individual changes in the blood pressure were analyzed, a 24 .+-. 4 mm Hg reduction of blood pressure was seen with nifedipine and saralasin compared to a -13 .+-. 1 mm Hg response, P < 0.05, to saralasin alone. Apparently, lowering SCa by EDTA in renovascular hypertension reduces MAP directly. Reduction of SCa results in a greater vasodepressor response to saralasin. Nifedipine has a synergistic effect when used with saralasin to lower blood pressure in renovascular hypertension.