Calcium chelation and calcium-channel blockade in anesthetized acute renovascular hypertensive dogs.
Acute animal studies were conducted to explore the effect of calcium 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 calcium (SCa) levels, while nifedipine was infused intravenously to antagonize calcium 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 to 137 +/- 6 mm Hg (p less than 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 less than 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 less than 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 less than 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 less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
D000758:Anesthesia; D000804:Angiotensin II / Q000037:antagonists & inhibitors; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000097:blood / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004285:Dogs; D004347:Drug Interactions; D004492:Edetic Acid / Q000494:pharmacology; D006978:Hypertension, Renovascular / Q000503:physiopathology*; D009543:Nifedipine / Q000494:pharmacology; D012083:Renin / Q000097:blood; D012504:Saralasin / Q000494:pharmacology
D002121:Calcium Channel Blockers; D000804:Angiotensin II; D004492:Edetic Acid; D012083:Renin; D012504:Saralasin; D009543:Nifedipine; D002118:Calcium