Effects of chronic treatment with a low dose of nicorandil on the function of the rat aorta during ageing.
1. It is known that ATP-sensitive potassium (K(ATP)) channels regulate the membrane potential of smooth muscle cells and vascular tone. Because their activity is altered during ageing, many pharmacological treatments aimed at improving K(ATP) channel and cardiovascular functions have been evaluated. Nicorandil, a K(ATP) channel opener, nitric oxide (NO) donor and anti-oxidant, induces vasodilation, decreases blood pressure and exhibits cardioprotection in ageing, as well as after ischaemia-reperfusion. 2. In the present study, using tension myography and biochemical and histological techniques, we investigated the effects of chronic (2 months) low-dose nicorandil (0.1 mg/kg per day) treatment on the function of rat aorta during ageing (in 4-, 12- and 24-month old rats). 3. The results showed that chronic nicorandil treatment significantly improves mechanical relaxation and noradrenaline-induced vasoconstriction in aged rats. At all ages, the nicorandil-induced vasodilation was primarily mediated by its NO donor group. Nicorandil treatment resulted in an additional 0.5-1 elastic lamella in the aorta and decreased total protein, collagen and elastin content in the aortic wall at all ages. However, in 4-month-old rats, nicorandil significantly increased the elastin : total protein ratio by 19%. 4. In contrast with results of previous studies that used high doses of nicorandil (i.e. 60 mg/kg per day), low-dose nicorandil treatment in the present study did not lead to a progressive desensitization to nicorandil and may be beneficial in improving arterial function in ageing or cardiovascular diseases.
Raveaud
Stéphanie
S
Laboratory of Vascular Physiopathologies: Cellular Interactions, Signalling and Ageing, Joseph Fourier University, Grenoble, F-38041, France.
Mezin
Paulette
P
Lavanchy
Nicole
N
Starcher
Barry
B
Mecham
Robert P
RP
Verdetti
Jean
J
Faury
Gilles
G
D000375:Aging / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D001696:Biomechanical Phenomena / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D004549:Elastin / Q000378:metabolism; D005260:Female; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D020108:Nicorandil / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects
D000959:Antihypertensive Agents; D009536:Niacinamide; D020108:Nicorandil; C030731:N-(2-hydroxyethyl)nicotinamide; D003094:Collagen; D004549:Elastin