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Hypotensive effect of calcium channel blockers is parallel with carbonic anhydrase I inhibition
1University of Medicine Oradea, Romanian Medical Academy of Sciences, Salaj.
Insights
Calcium channel blockers like verapamil and amlodipine strongly inhibit carbonic anhydrase I in both erythrocytes and vascular smooth muscles. This dual action, affecting calcium channels and enzyme activity, contributes to their blood pressure-lowering effects.
Area of Science:
- Biochemistry
- Pharmacology
- Physiology
Background:
- Calcium channel blockers (verapamil, amlodipine) are used to treat hypertension.
- Carbonic anhydrase I (CA I) is an enzyme found in erythrocytes and vascular smooth muscles.
- The role of CA I in vascular smooth muscle function and its interaction with calcium channel blockers is not fully understood.
Purpose of the Study:
- To investigate the in vitro and in vivo effects of verapamil and amlodipine on carbonic anhydrase I activity.
- To examine the impact of these drugs on arterial blood pressure in humans and animals.
- To elucidate a potential dual mechanism of action for calcium channel blockers involving CA I inhibition.
Main Methods:
- In vitro and in vivo studies were conducted.
- Assays were performed to measure carbonic anhydrase I activity in erythrocytes and vascular smooth muscle.
- Arterial blood pressure was monitored in human and animal subjects.
Main Results:
- Verapamil and amlodipine demonstrated strong inhibition of carbonic anhydrase I in both human erythrocytes and animal vascular smooth muscles.
- In hypertensive humans, calcium channel blockers reduced arterial blood pressure and erythrocyte CA I activity.
- A correlation was observed between drug-induced pH increase in vascular smooth muscle and inhibition of CA I.
Conclusions:
- Verapamil and amlodipine exhibit a dual mechanism of action in reducing blood pressure.
- The first mechanism involves direct calcium channel blockade.
- The second, proposed mechanism, involves the inhibition of vascular smooth muscle carbonic anhydrase I, leading to a pH increase that may influence calcium influx and contribute to the hypotensive effect.
Abstract:
In this article we studied in vitro and in vivo the effect of calcium channel blockers (verapamil and amlodipine) on erythrocyte carbonic anhydrase I activity, on carbonic anhydrase I isolated from vascular smooth muscles, and on arterial blood pressure values in human beings and in animals. Our in vitro and in vivo results have shown that verapamil and amlodipine are strong inhibitors of carbonic anhydrase I both in erythrocytes (in human beings) and in vascular smooth muscles (in animals). In human beings calcium channel blockers reduce arterial blood pressure in subjects with hypertension and progressively reduce erythrocyte carbonic anhydrase I activity. We assume that verapamil and amlodipine possess a dual mechanism of action: the first mechanism consists of their action on calcium channels, and the second mechanism, proposed by us, shows that verapamil and amlodipine inhibit vascular smooth muscle carbonic anhydrase I activity with consecutive pH increase. The increase of pH might be an additional factor involved in intracellular calcium influx through calcium channels. This dual mechanism of action would bring new data regarding the hypotensive effect of verapamil and amlodipine, effects that might also be parallel and dependent on carbonic anhydrase I inhibition.