THE EFFECTS OF PERINDOPRIL ON VASCULAR SMOOTH-MUSCLE POLYPLOIDY IN STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS

Objective: To quantify vascular smooth muscle polyploidy and growth ki netics in aortic cells from stroke-prone spontaneously hypertensive ra ts (SHRSP) and from normotensive Wistar-Kyoto (WKY) rats, and to exami ne the effects of treatment with the angiotensin converting enzyme (AC E) inhibitor perindopril on these parameters. Design: The following ex perimental groups were used: young (age <20 weeks) and old (age >20 we eks) untreated WKY rats and untreated SHRSP; SHRSP treated with perind opril, and age- and sex-matched control SHRSP; and SHRSP treated with hydralazine and hydrochlorothiazide and age- and sex-matched control S HRSP. The effects of treatment of the SHRSP with perindopril for 30 da ys on vascular smooth muscle polyploidy and growth kinetics were measu red and compared with the effects of equivalent antihypertensive doses of hydralazine and hydrochlorothiazide. Methods: Vascular smooth musc le polyploidy was measured using flow-cytometry DNA analysis of freshl y harvested cells. Growth curves were performed on cultured aortic cel ls. Plasma renin activity was measured by an antibody-trapping method, plasma angiotensin II (Ang II) by radioimmunoassay and plasma ACE act ivity by a colorimetric method. Cardiac hypertrophy was evaluated by m easuring the heart weight:body weight and left ventricle + septum weig ht:body weight ratios. Results: The SHRSP had markedly and significant ly elevated G(2) + M phase of the cell cycle. Treatment with perindopr il resulted in a significant reduction in polyploidy in the SHRSP, whe reas treatment with hydralazine and hydrochlorothiazide had no effect on the percentage of cells in the G(2) + M phase of the cell cycle. Th e regression of polyploidy after treatment with perindopril was associ ated with a significant reduction in the concentration of Ang II and A CE activity, and with a significant regression of cardiac hypertrophy. Increased mitogenesis of cultured vascular smooth muscle cells from t he SHRSP was not altered by treatment with perindopril. Conclusions: A CE inhibition reduces vascular smooth muscle polyploidy in large condu it arteries. This type of vascular protection is mediated by the reduc ed Ang II and possibly by increased kinins level, rather than by the h ypotensive effect alone.