Metabolic and cardiovascular responses to prolonged noradrenaline load and their antagonism by beta blockade in the rat.

Rats were given daily injections of noradrenaline (0.5 mg/kg), alprenolol (20 mg/kg), or both together for 17 to 39 days. Noradrenaline injections increased the size of the heart, interscapular brown adipose tissue (ISBAT) and, when the injections were given at a thermoneutral environment, the metabolic activity of the ISBAT. Alprenolol injections tended to reduce the size of the heart and ISBAT and, at a thermoneutral environment, metabolic activity of the skeletal muscle. Furthermore, noradrenaline treatment improved tolerance against body cooling in water at 25 degrees C and enhanced calorigenic response to injected noradrenaline. The metabolic alterations in the rats injected with both drugs together resembled more those of the animals injected with alprenolol only than those of the noradrenaline treated rats. It can be thus concluded that alprenolol, when given together with noradrenaline, antagonized noradrenaline-induced metabolic alterations in the organism. However, the increased pressor response to infused noradrenaline, which was evident in the alprenolol treated animals, was not seen in the animals treated with both drugs. By contrast, these animals, like also the noradrenaline-treated animals, showed decreased pressor response to noradrenaline. This finding suggests that prolonged beta blockade does not abolish the decreased sensitivity of alpha-adrenoreceptors following prolonged noradrenaline load. On the other hand, the hypotonic response to a beta adrenergic drug, isoprenaline, was reduced by prolonged beta blockade despite simultaneous noradrenaline injections.