Vasodilators inhibit acute alpha 1-adrenergic receptor-induced trophic responses in the vasculature.
Cardiovascular hypertrophy plays an important role in the development and maintenance of hypertension. Hyperactivity of the sympathetic nervous system may be one of the initiating factors responsible for the stimulation of growth processes involved in these structural alterations. We have used a well-established early biochemical marker of cellular growth processes, induction of ornithine decarboxylase (ODC), to determine whether alpha 1-adrenergic receptor-induced vascular trophic responses are dependent on arterial pressure elevation. Hydralazine or felodipine were coadministered to control the alpha 1-adrenergic receptor agonist-induced rise in mean arterial pressure (MAP). Methoxamine (2, 5, or 10 mg/kg s.c.) increased the average MAP (up to 20 mm Hg) and vascular ODC activity (up to ninefold) above control rats over 4 hours. Concomitant administration of hydralazine (0.5, 1.25, or 5 mg/kg s.c.) or felodipine (100 or 250 micrograms/kg s.c.) with methoxamine (10 mg/kg) attenuated the alpha 1-adrenergic receptor-induced activation of ODC in the aorta and mesenteric resistance vasculature, as well as the MAP increases. Vasodilators alone did not lower basal vascular ODC activity. The major findings include: 1) alpha 1-adrenergic receptor activation dose-dependently induces vascular ODC activity concomitantly with MAP elevation, 2) vasodilators inhibited both the alpha 1-adrenergic receptor-induced MAP increases and the activation of mesenteric vascular and aortic ODC, and 3) the stimulus-response correlation between MAP elevation and mesenteric (r = 0.78) and aortic (r = 0.92) ODC activation was characterized by a logistic function.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario, Canada.
K E
KE
Thompson
P
P
Friberg
M A
MA
Adams
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D004338:Drug Combinations; D015736:Felodipine / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006830:Hydralazine / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D008729:Methoxamine / Q000494:pharmacology; D009955:Ornithine Decarboxylase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D004338:Drug Combinations; D011942:Receptors, Adrenergic, alpha; D014665:Vasodilator Agents; D006830:Hydralazine; D009955:Ornithine Decarboxylase; D008729:Methoxamine; D015736:Felodipine