Increased alpha 1-adrenergic vascular sensitivity during development of hypertension in conscious dogs.
The goal of this study was to determine whether enhanced vascular responsiveness during the development of perinephritic hypertension is selective or nonspecific. The effects of graded infusions of norepinephrine (NE), phenylephrine (PE), angiotensin II (ANG II), and vasopressin (VP) were examined on mean arterial pressure, total peripheral resistance (TPR), and aortic pressure-diameter relationships in conscious dogs. NE increased TPR significantly greater (P < 0.01) in hypertension than normotension, as did PE infusion, whereas ANG II and VP increased TPR similarly before and after hypertension. Analysis of aortic pressure-diameter relationships also demonstrated significant (P < 0.05) shifts in response to NE and PE, but not ANG II and VP, during the development of hypertension. In normotensive dogs, low doses of ANG II infusion also enhanced the vasoconstrictor response not only to NE and PE but also to VP. In contrast to what was observed in hypertension, in the presence of ANG II infusion after ganglionic blockade, enhanced responses to PE and NE were no longer observed. The alpha 1-adrenergic receptor density in membrane preparations from aortic tissue, as determined by [3H]prazosin binding, was higher (P < 0.05) in hypertensive dogs than control dogs. Thus the vascular responsiveness in the aorta and resistance vessels is enhanced to alpha 1-adrenergic stimulation, but not to all vasoconstrictors, during developing perinephritic hypertension. The mechanism appears to involve increased alpha 1-adrenergic receptor density.
Uemura
N
N
Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston 02115.
Vatner
D E
DE
Shen
Y T
YT
Wang
J
J
Vatner
S F
SF
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000502:physiology / Q000648:ultrastructure; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000737:chemistry / Q000502:physiology / Q000648:ultrastructure; D003243:Consciousness / Q000502:physiology*; D004285:Dogs; D005260:Female; D006973:Hypertension / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000032:analysis / Q000502:physiology*; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014667:Vasopressins / Q000494:pharmacology
D011942:Receptors, Adrenergic, alpha; D014667:Vasopressins; D000804:Angiotensin II; D010656:Phenylephrine; D011224:Prazosin