Attenuated Aortic Vasodilation and Sympathetic Prejunctional Facilitation in Epinephrine-Deficient Mice: Selective Impairment of β₂-Adrenoceptor Responses

Abstract

It has been suggested that there is a link between epinephrine synthesis and the development of b 2 -adrenoceptor-mediated effects, but it remains to be determined whether this development is triggered by epinephrine. The aim of this study was to characterize b-adrenoceptor-mediated relaxation and facilitation of norepinephrine release in the aorta of phenylethanolamine-Nmethyltransferase-knockout (Pnmt-KO) mice. Catecholamines were quantified by reverse-phase high-performance liquid chromatography-electrochemical detection. Aortic rings were mounted in a myograph to determine concentration-response curves to selective b 1 -or b 2 -adrenoceptor agonists in the absence or presence of selective b 1 -or b 2 -adrenoceptor antagonists. Aortic rings were also preincubated with [ Isoproterenol and terbutaline induced concentration-dependent increases in tritium overflow in WT mice only. b 2 -Adrenoceptor protein density was decreased in membrane aorta homogenates of Pnmt-KO mice, and this finding was supported by immunofluorescence confocal microscopy. In conclusion, epinephrine is crucial for b 2 -adrenoceptor-mediated vasodilation and facilitation of norepinephrine release. In the absence of epinephrine, b 2 -adrenoceptor protein density was decreased in aorta cell membranes, thus potentially hindering its functional activity.

Adrenaline: More than a century after its discovery and still a mystery

“…It might be related to an impaired dobutamine-induced vasodilation through β 2 -adrenergic receptors. This hypothesis is supported by Moreira-Rodrigues et al, who observed that Pnmt-KO mice present a lower β 2 -adrenoceptor protein density in aorta cell membranes than their WT counterparts [8]. Another possibility for the blunted response to dobutamine is a decrease in myocardial contractile reserve.…”

“…Only more recently, was an adrenaline-deficient mouse model generated by selectively knocking out the Pnmt gene (Pnmt-KO) [3]. This animal cannot produce adrenaline, but is able to synthesize and maintain normal plasma levels of noradrenaline [5,8]. Studies have shown that Pnmt-KO mice survive to adulthood and breed effectively [3].…”

“…As pointed out by the authors, an increase in afterload may be involved in the marked hypertrophy. Since adrenaline stimulation of β 2 -adrenoceptors is more potent than that induced by noradrenaline, and Pnmt-KO mice present lower vasodilator β 2 -adrenoceptor density [8], Pnmt-KO mice may have been subjected to higher blood pressure during chronic exercise. In fact, it has previously been shown that Pnmt-KO mice develop higher blood pressure during acute exercise than WT mice [5].…”

Propranolol Reduces Cardiac Index But does not Adversely Affect Peripheral Perfusion in Severely Burned Children

“…Burns are associated with a high concentration of circulating levels of the catecholamines epinephrine and norepinephrine (27). Epinephrine has been shown to be responsible for β2-adrenoceptor-mediated vasodilation in an animal study (14). Thus, we postulate that propranolol, a non-selective β1-, β 2-adrenoceptor antagonist, is able to inhibit the epinephrine-induced vasodilatation and cause vasoconstriction, resulting in an increased SVRI in pediatric burn patients.…”

“…These findings were confirmed in another trial with 11 healthy normotensive male subjects (13). This elevation in SVRI is postulated to be β2-adrenoceptor-mediated (12,14). Hence, propranolol may affect SVRI in severely burned children.…”