NITRATE TOLERANCE AND AGING IN ISOLATED RAT AORTA

The purpose of this study was to determine whether there are age-relat ed changes in the extent of in vitro-induced nitrate tolerance. Nitrog lycerin pre-exposure (10 AM for 30 min) provoked a significant shift t o the right of the dose-response curve to nitroglycerin in aortae isol ated from rats of 8 weeks, 12 and 18 months. However, this shift to th e right was significantly larger at 18 months, both when KCl or phenyl ephrine were used as contractile agents. On the contrary, nitroglyceri n pre-exposure did not significantly alter the dose-dependent relaxati on to Sin-1 (3-morpholinosydnonimine, the active metabolite of molsido mine) at 8 weeks, 12 and 18 months. These data indicate that the exten t of the in vitro-induced nitrate tolerance is larger when aortae are isolated from senescent rats. This increase in tolerance does not appe ar to involve desensitization of guanylate cyclase.