Pathophysiological background for the use of calcium antagonists.
Correlation between blood pressure (BP) and total peripheral vascular resistance (TPR), hypotensive mechanisms of calcium antagonists, and cardiovascular responses to norepinephrine with and without administration of calcium antagonists were investigated in normotensive and genetic essential hypertensive humans. Supine resting decreased BP, heart rate (HR), stroke volume (SV), and cardiac output (CO), and, in contrast, it increased TPR. After 1 h supine rest, BP was positively correlated with TPR (r = 0.710; number = 45, p less than 0.001), but it was not correlated with CO. Intravenous infusion of the calcium antagonist diltiazem lowered BP and TPR, without apparently affecting HR, SV, and CO. In contrast, the calcium antagonist nifedipine diminished BP and TPR while increasing HR, SV, and CO. Norepinephrine elevated BP and TPR and decreased HR, SV, and CO. Prior administration of nifedipine inhibited elevation of TPR after treatment with norepinephrine. In contrast, prior administration of propranolol did not inhibit norepinephrine-induced BP and TPR elevation. From the results it may be concluded that elevation of BP is dependent on alteration of TPR, but not CO, in essential hypertensive humans. The arterial vasodilating effects of calcium antagonists induce a fall in both TPR and BP and inhibit norepinephrine-induced TPR increase. This suggests that abnormal contraction and relaxation of systemic arterial smooth muscle is a primary cause of the development and persistence of high BP in genetic (main gene) essential hypertensive humans.
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Aoki
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Sato
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects*; D014665:Vasodilator Agents
D002121:Calcium Channel Blockers; D014665:Vasodilator Agents; D004110:Diltiazem; D009638:Norepinephrine