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Platelet-activating effect of low-density lipoprotein and its reversal by isradipine
N Fetkovská1, V Fedelesová, M Kozlovský
1Department of Clinical Pharmacology, Medical Bionics Research Institute, Bratislava, Czechoslovakia.
Insights
The calcium channel blocker isradipine significantly reduced platelet aggregation in hypertensive patients. This drug may offer thrombovascular protection by restoring impaired platelet responses to serotonin and low-density lipoprotein (LDL).
Area of Science:
- Cardiology
- Pharmacology
- Hematology
Background:
- Essential hypertension is associated with impaired platelet function.
- Platelet aggregation plays a key role in thrombovascular events.
- Low-density lipoprotein (LDL) can amplify platelet aggregation.
Purpose of the Study:
- To investigate the effect of isradipine on platelet aggregation in patients with essential hypertension.
- To determine if isradipine alters platelet response to serotonin and LDL.
- To assess the potential thrombovascular protective mechanisms of isradipine.
Main Methods:
- A randomized, placebo-controlled study was conducted in 17 nonsmoking patients with essential hypertension.
- Platelet aggregation was measured ex vivo using serotonin and LDL as inducers.
- Measurements were taken after a placebo period and after 4 and 12 weeks of isradipine treatment.
Main Results:
- Isradipine significantly decreased serotonin-induced and LDL plus serotonin-induced platelet aggregation after 4 weeks compared to placebo.
- The amplifying effect of LDL on serotonin-induced aggregation was observed at baseline and during isradipine treatment.
- After 12 weeks, isradipine further reduced LDL plus serotonin-induced aggregation, eliminating the LDL amplification effect.
Conclusions:
- Isradipine treatment restores the impaired platelet response to serotonin and LDL in hypertensive patients.
- The inhibition of platelet aggregation by isradipine may represent a cellular mechanism for thrombovascular protection.
- Isradipine shows promise in managing hypertension-related thrombovascular risks.
Abstract:
The effect of the calcium antagonist isradipine on platelet aggregation (induced ex vivo by serotonin and low-density lipoprotein [LDL]) was studied in 17 nonsmoking patients with essential hypertension. Platelet aggregation was measured after a four-week placebo period, and after four and 12 weeks of treatment with isradipine. Both the serotonin-induced and the LDL plus serotonin-induced platelet aggregation were significantly decreased after four weeks of isradipine treatment compared with placebo. The amplifying effect of LDL on the serotonin-induced aggregation was significant both after placebo and after active treatment with isradipine. A further decrease in platelet aggregation induced by LDL plus serotonin was observed after 12 weeks of isradipine treatment so that no amplification of serotonin-induced aggregation by LDL could be detected. In conclusion, it appears that treatment with isradipine restores the impaired platelet response to serotonin and LDL in hypertensive patients. The inhibition of this response may represent a cellular mechanism of thrombovascular protection.