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American Journal of Pathology, Vol 148, 281-290, Copyright © 1996 by American Society for Investigative Pathology

REGULAR ARTICLES

Spontaneously hypertensive rats develop pulmonary hypertension and hypertrophy of pulmonary venous sphincters

S Aharinejad, DE Schraufnagel, P Bock, CA MacKay, EK Larson, A Miksovsky and SC Marks Jr
Department of Cell Biology, University of Massachusetts Medical Center, Worcester, USA.

This study explored the spontaneously hypertensive rat as an animal model of pulmonary hypertension and sought to identify anatomic changes in its pulmonary microvasculature, especially focal constrictions of pulmonary veins (sphincters). The average systemic and pulmonary artery blood pressures were 172/139 (+/- 9/9) and 36/14 (+/- 4/3), respectively, for spontaneously hypertensive Wistar Kyoto rats (SHR), and 134/83 (+/- 8/2) and 20/10 (+/- 2/2) for normotensive Wistar Kyoto rats (WKY) (P < 0.01 for both). Light microscopy of the lungs in SHR showed muscularization of both arteries and veins, but this was more pronounced in the small pulmonary veins. Perivascular edema was also present. There were 20 (+/- 4) leukocytes per 100 microns of capillary length in SHR and 9 (+/- 2) in WKY (P < 0.001). Transmission electron microscopy showed focal venous smooth muscle was greater in SHR than in WKY. Scanning electron microscopy of vascular casts showed the average maximal focal venous contraction (sphincter) was 54% (+/- 10) of its diameter in SHR, but was only 6% (+/- 4) in WKY (P < 0.01). Arterial contraction occurred in the hypertensive rats as bourglass narrowings of the casts, but was less conspicuous than venous constrictions. The mean alveolar capillary diameter was 8.1 microns (+/- 1.6) in SHR, compared with 6.3 microns (+/- 1.0) in WKY (P < 0.01). The central interspace between capillaries was 3.2 microns (+/- 1.6) in SHR and 6.0 microns (+/- 3.6) in WKY (P < 0.01). The venous contraction, capillary size, and capillary interspace distance correlated with the pulmonary blood pressure. The spontaneously hypertensive rat can be a model of pulmonary hypertension with its most notable structural change being increased muscularity in the small pulmonary veins.

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