Evidence for lack of innervation of beta-2 adrenoceptors in the blood vessels of the gracilis muscle of the dog.

Abstract

Cardiac /S-l adrenoceptors respond to sympathetic nerve stimulation (SNS), but it is not clear that SNS evokes fi-2 adrenoceptor-mediated vasodilation. Sensitivity of B adrenoceptors to catecholamines and to SNS was evaluated in dogs. Norepinephrine (NE) and epinephrine (E) were equipotent vasoconstrictors (femoral artery blood flow or gracilis autoperfusion pressure) before aadrenoceptor blockade with dibozane (DIB). After DIB, NE was 1/100 as potent a vasodilator as E, which was equipotent with isoproterenol (ISO). SNS evoked gracilis muscle vasoconstriction before DIB and vasodilation after. Dilation induced by SNS or acetylcholine (ACH) after DIB was blocked by atropine (AT), but that caused by NE was not. Dilation evoked by NE, E, or I after DIB and AT was blocked by propranolol (PROP). Vasoconstrictor responses to NE, E, or SNS in dogs without DIB were not augmented by PROP at a dose that blocked the dilator effect of ISO. NE and E were equipotent and both 1/10 as potent as ISO as positive inotropic and chronotropic agents. Cardiac responses to NE, E, ISO, and SNS were antagonized by PROP. Subclassification of adrenoceptors that subserve cardiac stimulation as fi-1 and that subserve vasodilation as fi-2 was substantiated. Cardiac fi-1 adrenoceptors responded to SNS and to circulating E and NE. Vascular fi-2 adrenoceptors responded to circulating E, to ISO, and to high doses of NE, but not to SNS. fi-2 Adrenoceptors in blood vessels appear not to be innervated and may function as hormone receptors sensitive primarily to E released from the adrenal medulla, rather than to NE released from adrenergic nerves.

Pulmonary vasodilator responses to catecholamines and sympathetic nerve stimulation in the cat. Evidence that vascular beta-2 adrenoreceptors are innervated.

“…The present data for the pulmonary vascular bed are in agreement with previous studies in skeletal muscle, liver, spleen, and adipose tissue and in isolated facial vein of the rabbit and support the hypothesis that norepinephrine liberated from sympathetic nerves can act on y8-2 receptors in blood vessels (Ngai et al, 1966;Viveros et al, 1968;Greenway et al, 1968;Greenway and Lawson, 1969;Jarhult, 1974, 1976;Pegram et al, 1976). However, other investigators have not been able to elicit vasodilator responses to adrenergic stimulation in a variety of organ systems (Glick et al, 1967;Rosell and Belfrage, 1975;Dawes and Falkner, 1975;Russell and Moran, 1980).…”

“…These data suggest that reversal of the response to nerve stimulation was not dependent on the type of a blocker employed and did not involve a cholinergic mechanism. The reasons for the difference in results in the present study and in the studies of Russell and Moran (1980) are uncertain but may suggest differences in nerve terminal-adrenergic receptor relationships in the skeletal muscle and the pulmonary vascular beds. The hypothesis that the feline pulmonary vascular bed is well supplied with /?…”

“…In the studies of Viveros et al (1968) responses to adrenergic stimulation were reversed after intraarterial administration of dibozane, a substance which is poorly soluble at neutral pH, whereas responses to nerve stimulation were not reversed by phentolamine. However, when dibozane was administered iv at a dose of 10 mg/kg, vasodilator responses to nerve stimulation were blocked by atropine (Russell and Moran, 1980). Moreover, results of the present study show that neuronally released norepinephrine can cause vasodilation and indicate that fi-2 receptors in the pulmonary vascular bed are innervated.…”

“…The hypotheses that vascular fi (fi-2) receptors are innervated and that neuronally released norepinephrine elicits vasodilation have been challenged recently (Russell and Moran, 1980). These investigators were unable to confirm the classic studies of Viveros et al (1968) that nerve stimulation caused atropine-insensitive vasodilation in skeletal muscle.…”

“…However, the concepts that /? adrenergic receptors in blood vessels are innervated and that neuronally released norepinephrine can elicit vasodilation by stimulating fi-2 receptors have been challenged recently (Russell and Moran, 1980). The present study was undertaken to investigate the actions of catecholamines and the nature of adrenergic receptors in the feline pulmonary vascular bed.…”