Related Experiment Videos
[Preclinical study of the action of a calcium channel blocker during salt load]
T Godfraind1, S Salomone, N Morel
1Laboratoire de Pharmacologie Faculté de Médecine, Université catholique de Louvain, Bruxelles.
Insights
Lacidipine treatment attenuated cardiovascular hypertrophy in salt-loaded rats, independent of blood pressure reduction. This antihypertensive drug also blunted vascular responsiveness to calcium channel activators.
Area of Science:
- Cardiovascular Physiology
- Pharmacology
- Hypertension Research
Context:
- Cardiovascular hypertrophy is a common complication of hypertension, but its relationship with hemodynamic and non-hemodynamic factors remains unclear.
- Standard antihypertensive drugs like hydralazine can lower blood pressure but do not always resolve cardiovascular hypertrophy.
- Stroke-prone rats (SHRSP) are utilized to investigate salt-dependent vascular changes and the effects of antihypertensive agents.
Purpose:
- To investigate the effects of lacidipine, a dihydropyridine calcium channel blocker, on salt-dependent cardiovascular hypertrophy and vascular reactivity in SHRSP.
- To determine if lacidipine's effects on hypertrophy are independent of its blood pressure-lowering actions.
- To characterize the impact of lacidipine on vascular responsiveness to calcium channel activators and explore potential mechanisms.
Summary:
- Lacidipine treatment in salt-loaded SHRSP attenuated cardiovascular hypertrophy, with a dose-dependent effect.
- Lower doses of lacidipine reduced hypertrophy without significantly lowering blood pressure, suggesting a blood pressure-independent effect.
- Lacidipine blunted the salt-induced increase in vascular responsiveness to the calcium channel activator Bay K 8644 in both basilar and mesenteric arteries.
Impact:
- Confirms lacidipine's blood pressure-independent effects on tissue remodeling in hypertension.
- Highlights the heterogeneous vascular response to salt loading and lacidipine treatment across different arterial beds.
- Suggests lacidipine's mechanism may involve inhibiting smooth muscle cell depolarization in mesenteric arteries, independent of endothelin pathways.
Abstract:
Cardiovascular hypertrophy is a common feature of hypertension, but it is not known if this is related only to increased blood pressure or also to non-hemodynamic factors. Indeed, drug treatment of hypertension with hydralazine does reduce blood pressure but not cardiovascular hypertrophy. We used Stroke-prone rats (SHRSP) who are sensitive to salt load in order to better characterize the action of an antihypertensive agent on salt-dependent vascular hypertrophy and change in reactivity of calcium channels. SHRSP were submitted to salt load from 8 to 14 weeks of age with or without lacidipine, a long acting dihydropyridine. We observed that the cardiovascular hypertrophy was attenuated by lacidipine 0.3 mgkg-1 day-1 which did not change high blood pressure. The action of 1 mgkg-1 day-1 was higher on hypertrophy but, in addition, it reduced blood pressure. The salt-related increase in vascular responsiveness to the calcium channel activator Bay K 8644 was blunted by lacidipine treatment in both basilar and mesenteric arteries. By contrast with basilar artery, in mesenteric artery, this increased responsiveness was insensitive to bosentan, an endothelin antagonist but could be related to smooth muscle cell depolarization inhibited by lacidipine treatment. The present results confirm that lacidipine has blood pressure-independent effect on tissue remodeling in hypertension. They show that vascular response to salt is heterogeneous among vessels but is equally sensitive to lacidipine.