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Calcium influx blockers in the treatment of essential hypertension
Insights
Essential hypertension involves increased vascular resistance due to calcium (Ca2+). Calcium channel blockers effectively lower blood pressure in hypertensive patients, suggesting a new treatment approach based on age.
Area of Science:
- Cardiovascular Pharmacology
- Hypertension Research
- Clinical Therapeutics
Background:
- Essential hypertension is characterized by elevated vascular resistance, primarily regulated by intracellular calcium (Ca2+) concentration.
- Increased extracellular Ca2+ dependence for noradrenaline-induced contraction is observed in resistance vessels of hypertensive individuals.
- Ca2+-influx inhibitors demonstrate potent vasodilating effects, indicating their therapeutic potential.
Purpose of the Study:
- To investigate the role of calcium influx in essential hypertension.
- To evaluate the efficacy of calcium channel blockers in hypertensive patients.
- To explore age-based treatment strategies for hypertension.
Main Methods:
- Assessed the vasodilating response to verapamil in patients with essential hypertension compared to normotensive subjects.
- Correlated verapamil-induced vasodilation with plasma adrenaline levels.
- Administered verapamil and nifedipine acutely to measure blood pressure changes.
- Analyzed the correlation between blood pressure reduction and initial blood pressure/patient age.
Main Results:
- Verapamil showed enhanced vasodilation in hypertensive patients, correlated with adrenaline levels.
- Acute administration of verapamil and nifedipine significantly lowered blood pressure in hypertensive patients.
- Blood pressure reduction by Ca2+-channel blockers correlated positively with initial blood pressure and patient age.
- Combined therapy with beta-blockers and Ca2+-channel blockers proved effective for resistant hypertension.
Conclusions:
- Essential hypertension exhibits heightened Ca2+-influx-dependent vasoconstriction linked to sympathetic nervous system activity.
- Ca2+-channel blockers are effective antihypertensive agents, with efficacy influenced by initial blood pressure and age.
- A treatment strategy favoring Ca2+-channel blockers for older hypertensive patients and beta-blockers for younger ones is proposed.
- Combination therapy offers a promising approach for managing therapy-resistant hypertension.
Abstract:
Elevated vascular resistance is the key factor in most cases of essential hypertension. Vascular resistance is determined by the sarcoplasmatic concentration of free Ca2+. Experimental studies have shown an increased dependence for the noradrenaline-induced contraction on extracellular Ca2+ from the aorta to the small resistance vessels. This is in accordance with the potent vasodilating effect found with Ca2+-influx inhibitors in man. Furthermore, a selective enhancement of the vasodilating response to verapamil has been found in patients with essential hypertension as compared to normotensive subjects. The verapamil-induced vasodilation in the hypertensive patients was positively correlated to plasma adrenaline concentration. These findings suggest accentuated Ca2+-influx dependent vasoconstriction in essential hypertension, which is related to the activity of the sympathetic nervous system. Acute administration of verapamil and nifedipine results in a distinct fall in blood pressure in patients with essential hypertension but not in normotensive subjects. Generally, the percentage fall in blood pressure with Ca2+-channel blockers has been closely positively correlated to the initial blood pressure level and in an open study with 43 patients with essential hypertension the decrease in blood pressure to verapamil was also positively correlated to the age of patients. These data may provide the basis for a new treatment concept for essential hypertension proposing a Ca2+-channel blocker as the first choice for the older patients and a beta-adrenoceptor blocking agent as the first line drug for the younger patients. Combined treatment with a beta-adrenoceptor blocking agent and a Ca2+-channel blocker seems most efficient in normalizing blood pressure in many therapy-resistant hypertensive patients.