Scientific Contributions Vascular Hypertrophy in Renal Hypertensive Spontaneously Hypertensive Rats

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 growth properties in vivo. To test whether specific growth stimuli produce more extensive hypertrophy in SHR than WKY rats, we compared their cardiovascular growth responses to two-kidney, one clip renal hypertension. Six-week-old animals were subjected to either renal artery clipping or sham operation. Four weeks after renal artery clipping, there was a proportionately smaller rise in systolic blood pressure in SHR than WKY rats (21% and 44%, respectively); however, the overall level of systolic blood pressure achieved in the two rat strains differed by less than 10 mm Hg (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 rats; 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 cellular hypertrophy. Small and medium-sized arteries of the mesenteric vasculature were also hypertrophied in SHR, and the medial cross-sectional area increased by 63% and 114%, respectively, compared with increases of only 15% and The presence of cardiovascular hypertrophy is well demonstrated in both human and experimental hypertension and plays an important role in the maintenance of elevated blood pressure.In renal hypertension the "cardiovascular amplifiers" undoubtedly play an important homeostatic role in elevating arterial blood pressure to maintain adequate renal function. Cardiovascular hypertrophy and the associated amplifiers may not only develop in response to a sustained elevation in blood pressure but also in some circumstances appear to develop independently of any abnormal rise in blood pressure. For example, in spontaneously hypertensive rats (SHR) cardiovascular hypertrophy is present very early in development, and it has been suggested that this may play a role in initiating the hypertension. " However, although the early abnormal changes in cardiovascular structure in SHR have been carefully documented, the mechanisms responsible for these changes are yet to be defined. Received August 5, 1993; accepted in revised form March 23, 1994. From the Baker Medical Research Institute (R.J.D., A.B.) and Alfred-Baker Medical Unit (P.K., C.J.O.), Alfred Hospital, Prahran, Victoria, Australia. Correspondence to Dr R. Dilley, Baker Medical Research Institute, PO Box 348, Prahran 3181, Victoria, Australia. © 1994 American Heart Association, Inc. 23% in WKY rats. Strain differences between the shamoperated rat groups were small. In a hemodynamic analysis of the hindquarter 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 appeared smaller in SHR than WKY rats, and the increase in perfusion pressures 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 pressure could not account for this difference. Overall, this study indicates that the cardiovascular system of the SHR is more responsive to the hypertrophic stimuli of two-kidney, one clip renal hypertension. The more rapid and in some vessels more extensive hypertrophy that develops in SHR compared with WKY rats, despite only small differences in systolic blood pressure, supports the hypothesis that the stimulation of genes that contribute to the abnormal growth of vascular smooth muscle cells of the SHR may contribute to the development of vascular hypertrophy in these animals. (Hypertension. 1994;24:8-1S.)