Epinephrine and the genesis of hypertension.
Several lines of evidence suggest a psychophysiological link between stress, adrenomedullary activation, and the genesis of hypertension. Experimental data support four important concepts: 1) epinephrine stimulates prejunctional beta 2-adrenergic receptors that facilitate norepinephrine release from sympathetic nerve endings; 2) epinephrine can be converted into a cotransmitter by neuronal uptake and on subsequent release augment the simultaneous discharge of norepinephrine; 3) exogenous epinephrine can induce sustained hypertension in rats; and 4) there is a period of critical sensitivity to endogenous epinephrine in a genetic model of rat hypertension. Plasma epinephrine concentrations are elevated in many young subjects with borderline or mild hypertension. The hypothesis that intermittent surges in epinephrine could initiate or promote the development of primary hypertension by amplifying peripheral neurotransmission, both directly (facilitative effect) and indirectly (cotransmitter action), is supported by reports that hemodynamic and noradrenergic responses to sympathetic activation can be augmented by increases in endogenous epinephrine or by its local or systemic (up to 30 ng/kg/min) infusion. Such responses have been documented in both normotensive and hypertensive subjects and can be blocked by propranolol. Although the weight of evidence (mostly indirect) indicates that epinephrine can augment norepinephrine release in humans, the epinephrine hypothesis, itself, remains unproven. Expression of hypertension by this mechanism may be restricted to a specific epinephrine-sensitive subset of individuals with a genetic predisposition to high blood pressure.
Floras
J S
JS
Division of Cardiology, Toronto General Hospital, University of Toronto, Canada.
D000818:Animals; D002395:Catecholamines / Q000097:blood; D004837:Epinephrine / Q000502:physiology*; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000209:etiology*; D009638:Norepinephrine / Q000378:metabolism; D009994:Osmolar Concentration; D011942:Receptors, Adrenergic, alpha / Q000502:physiology
D002395:Catecholamines; D011942:Receptors, Adrenergic, alpha; D009638:Norepinephrine; D004837:Epinephrine