Reduction in aortic smooth muscle beta-adrenergic responsiveness results in enhanced norepinephrine responsiveness in the Dahl salt-sensitive rat.
In an earlier report we observed alterations in aortic smooth muscle alpha- and beta-adrenergic responsiveness in the Dahl rat. The present study was designed to define the time course of these changes and further characterize the alterations in this model of hypertension. Four-week-old male Dahl salt-sensitive (DS) rats were placed on either a normal (DSN) or high salt diet (8% NaCl; DSH). Aortic smooth muscle responsiveness was studied at 3 and 6 weeks of the dietary treatment. No differences were seen between the 2 groups in either the contractile response to KCl or the relaxation responses to sodium nitrite and acetylcholine. Isoproterenol-induced relaxation was significantly attenuated and contractile response to norepinephrine (NE) were enhanced at 3 weeks of treatment in DSH rats, however, no differences were seen between the 2 groups at 6 weeks. Since alterations were seen only at 3 weeks of treatment, aortic smooth muscle responsiveness to the specific alpha-agonists phenylephrine (alpha 1), guanfacine (alpha 2) and contractile responses to NE in the presence of propranolol were evaluated at three weeks. No differences were observed between the 2 groups with any of these treatments. Thus, it appears that the increased NE responsiveness seen in aortic smooth muscle of DSH rats during the developmental stage of the hypertension is the result of a decrease in beta-adrenergic responsiveness and not an increase in alpha-adrenergic responsiveness.
Soltis
E E
EE
Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville 32610.
Katovich
M J
MJ
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism*; D004032:Diet; D020022:Genetic Predisposition to Disease; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D011922:Rats, Mutant Strains; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D012965:Sodium Chloride / Q000008:administration & dosage; D014661:Vasoconstriction; D014664:Vasodilation
D011943:Receptors, Adrenergic, beta; D012965:Sodium Chloride; D009638:Norepinephrine