Nitrate tolerance and aging in isolated rat aorta.
The purpose of this study was to determine whether there are age-related changes in the extent of in vitro-induced nitrate tolerance. Nitroglycerin pre-exposure (10 microM for 30 min) provoked a significant shift to the right of the dose-response curve to nitroglycerin in aortae isolated from rats of 8 weeks, 12 and 18 months. However, this shift to the right was significantly larger at 18 months, both when KCl or phenylephrine were used as contractile agents. On the contrary, nitroglycerin pre-exposure did not significantly alter the dose-dependent relaxation to Sin-1 (3-morpholinosydnonimine, the active metabolite of molsidomine) at 8 weeks, 12 and 18 months. These data indicate that the extent of the in vitro-induced nitrate tolerance is larger when aortae are isolated from senescent rats. This increase in tolerance does not appear to involve desensitization of guanylate cyclase.
Unger
P
P
Cardiology Department, Hôpital Erasme, Brussels, Belgium.
Berkenboom
G
G
Brékine
D
D
Fontaine
J
J
D000375:Aging / Q000502:physiology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D066298:In Vitro Techniques; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D005996:Nitroglycerin / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D010656:Phenylephrine; C002385:linsidomine; D008981:Molsidomine; D005996:Nitroglycerin