Studies on the sensitization to cardiovascular effects of catecholamines.

Abstract

Wistar rats were given 20 daily injections of either isoproterenol (ISO) (30 μg/100 g/day), nor-adrenaline (NA) (30 μg/100 g/day), guanethidine (G) (15 mg/kg/day), or NA plus G together. Guanethidine, alone or in association with NA, increased the blood pressure and heart rate response to NA in the whole animal. Guanethidine alone had no effect on the inotropic effects of NA in isolated hearts. Beta receptor responses to NA were potentiated in the whole animal by chronic treatment with NA and in isolated hearts by chronic treatment with NA or ISO. Responses to ISO were also potentiated by treatment with guanethidine, noradrenaline, and isoproterenol. It was found also that guanethidine treatment reduced 3H-NA uptake by 50% but had no effect on 3H-ISO uptake and that NA and ISO treatments had no effect on the uptake of 3H-NA and 3H-ISO. Prolonged treatments with NA or ISO increased the sensitivity of the beta receptors, possibly as a result of the repeated stimulations by large doses of these stimulants. The sensitization of adrenergic receptors by guanethidine could result from both a reduced NA uptake and a direct action on smooth muscle fibers.