Neural and humoral mechanisms of angiotensin-dependent hypertension.
We examined whether neural or humoral mechanisms mediate the acute versus chronic phases of angiotensin II (ANG II)-dependent hypertension in rabbits. ANG II was administered intravenously at 50 ng.kg-1.min-1 for 10 days. This dose of ANG II elevated mean arterial pressure (MAP) from 76 +/- 2 to 98 +/- 2 mmHg on day 1 and sustained the hypertension throughout the infusion period. Heart rate (226 +/- 7 beats/min) was not altered. The depressor response to ganglionic blockade (-38 +/- 2 mmHg) was significantly blunted on day 1 (-22 +/- 3 mmHg) and was significantly enhanced on days 5 (-52 +/- 4 mmHg) and 7 (-52 +/- 6 mmHg). In contrast, plasma norepinephrine (PNE) and renal sympathetic nerve activity (RSNA) levels were acutely reduced to approximately one-third of control (day 1 of ANG II) and chronically rose to an intermediate level (2-9 days of ANG II). However, the pressor effect of resetting PNE and RSNA may be magnified by an augmented pressor responsiveness to alpha-agonists after chronic ANG II. In animals with the area postrema removed, PNE, RSNA, and heart rate were acutely reduced and remained chronically depressed. In addition, area postrema lesion blocked the chronic, but not the acute hypertensive response, to infusing ANG II. Thus the direct vasoconstrictor actions of ANG II appear to acutely predominate, whereas neurogenic vasomotor tone appears to chronically predominate. This shift appears to be mediated by changes in vascular sensitivity, as well as the area postrema allowing resetting of the baroreflex.
Department of Pharmacology, University of Texas Health Science Center, San Antonio 78284-7764.
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Bishop
D000804:Angiotensin II / Q000037:antagonists & inhibitors; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002552:Cerebral Ventricles / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005730:Ganglionic Blockers / Q000494:pharmacology; D006339:Heart Rate; D006973:Hypertension / Q000139:chemically induced*; D007668:Kidney / Q000294:innervation; D009424:Nervous System Physiological Phenomena; D009638:Norepinephrine / Q000097:blood; D010656:Phenylephrine / Q000494:pharmacology; D011817:Rabbits; D012504:Saralasin / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000502:physiology; D014294:Trimethaphan / Q000494:pharmacology
D005730:Ganglionic Blockers; D000804:Angiotensin II; D010656:Phenylephrine; D014294:Trimethaphan; D012504:Saralasin; D009638:Norepinephrine