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Pathophysiological background for the use of calcium antagonists
Insights
Blood pressure elevation in essential hypertension is linked to increased total peripheral vascular resistance (TPR), not cardiac output (CO). Calcium antagonists effectively lower blood pressure by reducing TPR and inhibiting norepinephrine-induced vasoconstriction.
Area of Science:
- Cardiovascular Physiology
- Pharmacology
Background:
- Essential hypertension is a complex condition with multifactorial causes.
- Understanding the relationship between blood pressure, vascular resistance, and cardiac output is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the correlation between blood pressure (BP) and total peripheral vascular resistance (TPR) in normotensive and hypertensive humans.
- To elucidate the hypotensive mechanisms of calcium antagonists.
- To examine cardiovascular responses to norepinephrine with and without calcium antagonists.
Main Methods:
- Investigated BP, heart rate (HR), stroke volume (SV), and cardiac output (CO) in normotensive and genetic essential hypertensive humans.
- Administered intravenous calcium antagonists (diltiazem, nifedipine) and norepinephrine.
- Analyzed cardiovascular responses before and after drug administration.
Main Results:
- BP was positively correlated with TPR (r = 0.710, p < 0.001) but not CO.
- Diltiazem lowered BP and TPR; nifedipine lowered BP and TPR while increasing HR, SV, and CO.
- Norepinephrine increased BP and TPR; prior nifedipine administration inhibited this TPR increase, while propranolol did not.
Conclusions:
- Elevated BP in essential hypertension is primarily dependent on alterations in TPR, not CO.
- Arterial vasodilating effects of calcium antagonists reduce TPR and BP.
- Abnormal systemic arterial smooth muscle function may be a primary cause of essential hypertension.
Abstract:
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.