[Preclinical study of the action of a calcium channel blocker during salt load].
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.
Godfraind
T
T
Laboratoire de Pharmacologie Faculté de Médecine, Université catholique de Louvain, Bruxelles.
Salomone
S
S
Morel
N
N
Ghisdal
P
P
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy*; D051381:Rats; D011918:Rats, Inbred SHR; D012965:Sodium Chloride / Q000494:pharmacology*
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C060285:lacidipine; D012965:Sodium Chloride
Etude préclinique de l'action d'un anticalcique lors d'un régime riche en sel.