Chronic treatment with the angiotensin I converting enzyme inhibitor, perindopril, protects in vitro carbachol-induced vasorelaxation in a rat model of vascular calcium overload.
1. Treatment of young rats with vitamin D3 plus nicotine produced 31 and 4 fold increases in the calcium content of the aorta and the mesenteric arterial bed, respectively. 2. Aortic rings and perfused mesenteric arterial beds from vitamin D3/nicotine-treated animals showed a diminished contractile response to noradrenaline in vitro. 3. In vascular preparations from vitamin D3/nicotine-treated animals, precontracted with noradrenaline, relaxation by the endothelium-dependent vasodilator, carbachol, was attenuated but responses to sodium nitroprusside were not modified. 4. Prolonged treatment with the angiotensin I converting enzyme inhibitor, perindopril, at a dose (1 mg kg-1) which did not significantly modify blood pressure, failed to prevent vascular calcium overload. 5. Perindopril treatment diminished noradrenaline-evoked vasoconstrictor responses of aortic rings in both groups, but restored responses in mesenteric arterial beds of vitamin D3/nicotine-treated rats. 6. Perindopril treatment also restored the maximal responses to carbachol of both aortic rings and mesenteric arterial beds of vitamin D3/nicotine-treated rats. 7. In conclusion, in the vitamin D3 plus nicotine model of calcium overload, reduced endothelial-mediated relaxation can be prevented by perindopril treatment.
Henrion
D
D
Laboratoire de Pharmacologie Cardio-vasculaire, Faculté de Pharmacie, Université de Nancy, France.
Chillon
J M
JM
Capdeville-Atkinson
C
C
Vinceneux-Feugier
M
M
Atkinson
J
J
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology*; D002217:Carbachol / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002762:Cholecalciferol / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D008274:Magnesium / Q000378:metabolism; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology; D009538:Nicotine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D020913:Perindopril; D051381:Rats; D011919:Rats, Inbred Strains; D013152:Splanchnic Circulation / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; D009599:Nitroprusside; D002762:Cholecalciferol; D009538:Nicotine; D002217:Carbachol; D008274:Magnesium; D002118:Calcium; D009638:Norepinephrine; D020913:Perindopril