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Calcium entry blockade and adrenergic vascular reactivity in hypertensives: differences between nicardipine and
R Pedrinelli1, G Panarace, A Salvetti
1Hypertension Unit, I Clinica Medica, University of Pisa, Italy.
Insights
Nicardipine and diltiazem, calcium entry blockers, affect forearm vascular responses differently in hypertensive patients. Nicardipine showed alpha-antagonism, while diltiazem interfered with beta-adrenergic mechanisms.
Area of Science:
- Cardiovascular Pharmacology
- Human Physiology
Background:
- Calcium entry blockers are widely used for hypertension.
- Understanding their specific vascular mechanisms is crucial.
Purpose of the Study:
- To investigate the forearm vascular effects of nicardipine and diltiazem.
- To compare their interactions with norepinephrine and beta-adrenergic pathways.
Main Methods:
- Infusion of nicardipine and diltiazem into the brachial artery in hypertensive patients.
- Evaluation of forearm vascular response to norepinephrine and isoproterenol.
- Assessment of drug interference with alpha- and beta-adrenergic receptor activity.
Main Results:
- Nicardipine increased forearm blood flow and dose-dependently antagonized norepinephrine's vasoconstrictor effect.
- Diltiazem potentiated norepinephrine responses, an effect abolished by propranolol.
- Diltiazem reduced vasodilation to isoproterenol, indicating interference with beta-adrenergic mechanisms.
Conclusions:
- Nicardipine exhibits functional alpha-antagonism in forearm vasculature.
- Diltiazem interferes with beta-adrenergic vasorelaxing mechanisms.
- These findings highlight the heterogeneity of calcium entry blockers in humans.
Abstract:
The interference of nicardipine and diltiazem infused into the brachial artery at systemically ineffective rates, with the forearm vascular response to graded exogenous norepinephrine, was evaluated in hypertensive patients. Nicardipine (1 and 3 micrograms/dl forearm tissue/min in both absence and presence of propranolol) increased forearm blood flow (venous plethysmography) and antagonized dose dependently the vasoconstrictor effect of norepinephrine, suggesting that functional alpha-antagonism may participate in the vasodilating and possibly the antihypertensive effect of the drug. On the contrary, no antagonism but rather potentiation of the responses to norepinephrine occurred after diltiazem (0.5 and 1 microgram/dl forearm tissue/min). Because intra-arterial propranolol abolished that potentiating action of the drug, whereas the local vasodilation to isoproterenol was clearly reduced, diltiazem probably interfered with beta-adrenergic receptor-mediated vasorelaxing mechanisms in human forearm arterioles. The data further stress the heterogeneity of calcium entry blockers in humans.