Date of Award

Winter 1997

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Program/Concentration

Biomedical Sciences

Committee Director

Russell L. Prewitt

Committee Member

Thomas J. Lauterio

Committee Member

Paul H. Ratz

Committee Member

Patricia B. Williams

Abstract

These studies were designed to characterize the relative roles of angiotensin II (ANG II) and pressure in the structural alterations that occur in experimental hypertension. Two separate studies were performed in order to differentiate these two mechanisms. First, male Wistar rats were subjected to one-kidney, one-clip (1K1C) hypertension or sham operation. Losartan, an AT1 receptor antagonist, was administered chronically to half of each surgical group beginning one day before the operation and continued until the end of the study. In a second experiment, rats were implanted with osmopumps delivering either ANG II or saline. To maintain pressure in the normotensive range, minoxidil, a vasodilator, was administered to half of each group one day before pump implantation and continued until the animals were sacrificed. In both experiments, systolic blood pressure was monitored and recorded throughout the two week study. Upon completion of both experimental periods, anesthetized rats were perfusion fixed in a vasodilated state and the thoracic aorta, carotid, small mesenteric and external spermatic arteries were extracted, fixed and processed. Morphological analysis revealed that cross-sectional wall area was correlated with elevated arterial pressure, but not with angiotensin II infusion or AT1 receptor activation. Immunohistochemical analysis indicated that vascular smooth muscle cell hypertrophy, not hyperplasia, contributed to the increase in cross-sectional wall area of the arteries. Also, capillary density was reduced in renal hypertension and this was not affected by AT1 receptor inhibition. In addition, PDGF-A mRNA was elevated in arterial walls of hypertrophied vessels. This effect was associated with elevated arterial pressure, but not with angiotensin II infusion. This PDGF-A expression was partially reduced by AT1 receptor inhibition in the small mesenteric artery.

These studies indicate that arterial hypertrophy in 1K1C hypertension and angiotensin II infusion occurs in response to elevated pressure. This arterial hypertrophy was not associated with hyperplasia or polyploidy of vascular smooth muscle cells. Capillary density is not affected by ANG II infusion, or AT1 receptor inhibition. In addition, PDGF-A expression is correlated with elevated pressure and arterial wall hypertrophy.

Comments

Dissertation submitted to the Faculty of Eastern Virginia Medical School and Old Dominion University in Partial Fulfillment of the Requirement for the Degree of Doctor of Philosophy in Biomedical Sciences.

DOI

10.25777/3sek-n857

ISBN

9780591623413

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