Role of presynaptic beta 2-adrenergic facilitation in the development and maintenance of DOCA-salt hypertension.
The present study evaluated the contribution of the presynaptic beta 2-adrenergic facilitation in the increase of plasma norepinephrine levels observed in deoxycorticosterone acetate (DOCA)-salt hypertension. Epinephrine is thought to be the major endogenous activator of this presynaptic mechanism and although basal epinephrine levels were similar in normotensive and DOCA-salt hypertensive rats, the sensitivity of the presynaptic beta 2-adrenergic facilitatory mechanism was found to be increased in hypertensive animals. This was shown in vivo by the enhanced plasma norepinephrine increases induced by a direct presynaptic stimulation with a selective beta 2-adrenergic receptor agonist. Furthermore, the adrenal medulla was hyperreactive in response to a hemorrhagic hypotension of 50 mm Hg, as shown by a greater plasma epinephrine increase in DOCA-salt-treated rats, and tissue concentrations of epinephrine were found to be greatly increased in the aorta of hypertensive animals. The possible contribution of epinephrine activation of the presynaptic beta 2-adrenergic mechanism on the development and maintenance of DOCA-salt hypertension was assessed by evaluating the effects of chronic or acute adrenalectomy, respectively. Acute adrenalectomy decreased significantly the blood pressure only in hypertensive animals, whereas chronic adrenalectomy abolished the plasma norepinephrine and blood pressure differences between normotensive and DOCA-salt-treated rats. The present results therefore suggest that the presynaptic beta 2-adrenergic facilitation is exaggerated in DOCA-salt hypertension, mainly due to an increased sensitivity of this mechanism and to a hyperreactivity of the adrenal medulla.(ABSTRACT TRUNCATED AT 250 WORDS)
Moreau
P
P
Groupe de Recherche sur le Système Nerveux Autonome, Faculté de Pharmacie, Université de Montréal, Québec, Canada.
Drolet
G
G
Yamaguchi
N
N
de Champlain
J
J
D000315:Adrenalectomy; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D003900:Desoxycorticosterone; D005280:Fenoterol / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006470:Hemorrhage / Q000503:physiopathology; D006830:Hydralazine / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018343:Receptors, Adrenergic, beta-2 / Q000502:physiology*; D017661:Receptors, Presynaptic / Q000502:physiology*; D012965:Sodium Chloride; D013564:Sympathetic Nervous System / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D011412:Propanolamines; D018343:Receptors, Adrenergic, beta-2; D017661:Receptors, Presynaptic; D009599:Nitroprusside; D005280:Fenoterol; D006830:Hydralazine; D003900:Desoxycorticosterone; D012965:Sodium Chloride; C026777:ICI 118551