Here, the influence of β3-adrenoceptors on
catecholamine release in normotensive and spontaneously hypertensive rats was analyzed. Blood pressure was recorded through a femoral artery
catheter, and cardiac output by ascending aorta flow. Time from onset of flow to maximum rise in flow indicated inotropy. Total peripheral vascular resistance (TPR) was calculated.
Norepinephrine release was stimulated with
tyramine, which allowed presynaptic release-control to be reflected as changes in the plasma
norepinephrine concentration. β3-adrenoceptor agonist (BRL37344) reduced baseline vascular resistance, the
tyramine-stimulated
norepinephrine overflow and the positive inotropic response to
tyramine in hypertensive but not normotensive rats. β3-adrenoceptor antagonist (
SR59230A) reduced
tyramine-stimulated
norepinephrine release in both strains and the secretion of
epinephrine in hypertensive rats.
SR59230A reduced
tyramine-induced
tachycardia in normotensive rats, and prevented down-regulation of the
tyramine-induced rise in resistance in hypertensive rats. It was concluded that the contradicting results obtained by agonist vs. antagonist, could be explained by their interaction with two different β-
adrenoceptors: The BRL37344-dependent inhibition of stimulated
norepinephrine release and positive inotropic response to
tyramine was compatible with stimulation of β3-adrenoceptor coupling to inhibitory
G-protein. This was observed only in hypertensive rats during stimulated, high levels of circulating
catecholamines. The effect of BRL37344 on baseline vascular resistance was compatible with activation of β3-adrenoceptor coupling to
endothelial nitric oxide synthase. The inhibitory effect of
SR59230A on
tyramine-stimulated
norepinephrine release in both strains, the increased TPR-response to
tyramine in hypertensive rats and
tachycardia in normotensive rats may result from inhibition of the low-affinity-state β1-adrenoceptor, also known as the putative β4-adrenoceptor.