AORTIC MEDIAL HYPERTROPHY IN SHRJOwens

tive in preventing SMC hypertrophy and hyperploidy than hyperplasia suggest that the signals for SMC hypertrophy are different from those for hyperplasia. However, the specific factors that stimulate aortic SMC hypertrophy and hyperploidy in the SHR are unclear. Three lines of indirect evidence indicate that SMC hypertrophy represents a response to increased blood pressure or wall stress: 1) Our laboratory-and others have consistently observed a high degree of correlation between the level of blood pressure and the frequency of polyploidism in a variety of hypertensive models. 2) Development of SMC hypertrophy and hyperploidy in aortas of SHR occurs predominantly after blood pressure has increased to its maximal level.' 6 3) Normalization of blood pressure in SHR with antihypertensive drug treatment is effective in preventing further development of SMC hypertrophy and hyperploidy, as well as in reversing some of the hypertrophic changes that have already occurred. Results of our drug treatment studies support a role for elevated blood pressure in the hypertrophic response of SMCs. However, this evidence is not compelling, since treatment was with a combination of three drugs (reserpine, chlorothiazide, and hydralazine), and it is not clear whether the effects of drugs were the direct result of lowering of blood pressure or due to some specific effect of one or more of the drugs on cellular growth. Thus, in the present investigation, we explored the role of elevated blood pressure on the development of SMC hypertrophy and hyperploidy in the SHR by examining the effects of various single antihypertensive drugs that have different primary mechanisms of action. We used captopril, a converting enzyme inhibitor"; hydralazine, a direct smooth muscle relaxant; and propranolol, a /3-adrenergic blocker. Our rationale was that if each of these drugs influences hypertrophy in proportion to its blood pressure-lowering effects, additional support would be provided for the hypothesis that hypertrophic vascular changes were secondary to elevated pressure. If, however, blood pressure effects and indices of hypertrophy were dissociated, the studies would suggest that factors other than or in addition to blood pressure were important and perhaps provide insight as to what those factors might be.