Effect of sodium balance and calcium channel blocking drugs on blood pressure responses.
To study the role of calcium movements in mediating the effects of sodium chloride on the response of blood pressure to angiotensin II (ANG II), we infused ANG II before and after giving calcium channel blocking drugs (nifedipine and diltiazem) and calcium infusions to normal subjects during high and low sodium intakes. ANG II was also in nine patients with essential hypertension eating a low sodium diet. In preliminary studies, the effects of nifedipine, 20 mg p.o., on blood pressure and plasma renin activity were determined. Sensitivity to infused ANG II was calculated as the slope of the linear regression of the increase in diastolic blood pressure (DBP) expressed as a function of the ANG II infusion rate (mm Hg/ng ANG II/kg/min). During intake of a high sodium diet (Na, 200 mEq/day) both drugs significantly (p less than 0.05) reduced ANG II sensitivity, while on a low sodium diet (10 mEq Na), neither drug reduced ANG II sensitivity. There was a significant (p less than 0.001) inverse correlation between the initial ANG II-DBP sensitivity and the change in sensitivity induced by the calcium channel blocking drugs in normal subjects (r = -0.78) and in hypertensive patients (r = -0.70). Five hypertensive patients had greater than normal ANG II-DBP sensitivity that was significantly (p less than 0.05) reduced by nifedipine. Calcium infusion did not affect the ANG II-DBP sensitivity on either diet. The results suggest that in normal subjects increased DBP responses to ANG II, induced by an increase in sodium intake, are partially mediated by increased extracellular to intracellular calcium movements, since they are blocked by the structurally different calcium channel blocking drugs nifedipine and diltiazem. In hypertensive patients on a low sodium diet, increased DBP responses to ANG II infusion were blocked by nifedipine, indicating they are at least partly mediated by increased extracellular to intracellular calcium flux.
D000328:Adult; D000804:Angiotensin II / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004039:Diet, Sodium-Restricted; D004110:Diltiazem / Q000494:pharmacology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism*
D002121:Calcium Channel Blockers; D000804:Angiotensin II; D012964:Sodium; D004110:Diltiazem; D009543:Nifedipine; D002118:Calcium; D009638:Norepinephrine