VASCULAR HYPERTROPHY IN RENAL HYPERTENSIVE SPONTANEOUSLY HYPERTENSIVERATS

Vascular smooth muscle cells isolated from spontaneously hypertensive rats (SHR) replicate faster in vitro than do cells from Wistar-Kyoto ( WKY) rats, suggesting that the vascular hypertrophy seen early in the life of SHR might be at least partially caused by abnormal cellular gr owth properties in vivo. To test whether specific growth stimuli produ ce more extensive hypertrophy in SHR than WKY rats, we compared their cardiovascular growth responses to two-kidney, one clip renal hyperten sion. Six-week-old animals were subjected to either renal artery clipp ing or sham operation. Four weeks after renal artery clipping, there w as a proportionately smaller rise in systolic blood pressure in SHR th an WKY rats (21% and 44%, respectively); however, the overall level of systolic blood pressure achieved in the two rat strains differed by l ess than 10 mmHg (4%). Limitations in the blood pressure responses of SHR to renal artery clipping were not due to inadequate development of left ventricular hypertrophy, as this was greater in SHR than WKY rat s; however, aortic hypertrophy was similar in both strains. Aortic DNA content changes in SHR were consistent with a significant hyperplasia of medial smooth muscle cells, whereas in WKY rats, there was cellula r hypertrophy. Small and medium-sized arteries of the mesenteric vascu lature were also hypertrophied in SHR, and the medial cross-sectional area increased by 63% and 114%, respectively, compared with increases of only 15% and 23% in WKY rats. Strain differences between the shamop erated rat groups were small. In a hemodynamic analysis of the hindqua rter vasculature performed under constant flow conditions, an increase in vascular resistance was consistent with encroachment of the vessel wall on the lumen. Average hindquarter vascular lumen diameter appear ed smaller in SHR than WKY rats, and the increase in perfusion pressur es during maximal constriction with methoxamine plus angiotensin II in both rat strains also suggested significant vessel wall hypertrophy, The increase in perfusion pressure at maximal constriction was greater in SHR than WKY rats, and the absolute level of systolic blood pressu re could not account for this difference. Overall, this study indicate s that the cardiovascular system of the SHR is more responsive to the hypertrophic stimuli of two-kidney, one dip renal hypertension. The mo re rapid and in some vessels more extensive hypertrophy that develops in SHR compared with WKY rats, despite only small differences in systo lic blood pressure, supports the hypothesis that the stimulation of ge nes that contribute to the abnormal growth of vascular smooth muscle c ells of the SHR may contribute to the development of vascular hypertro phy in these animals.