VASCULAR SMOOTH-MUSCLE POLYPLOIDY IN GENETIC-HYPERTENSION - THE ROLE OF ANGIOTENSIN-II

Flow cytometry DNA analysis has been used to measure the percentage of aortic vascular smooth muscle cells in G(2) + M phase of the cell cyc le in mature stroke-prone spontaneously hypertensive rats (SHRSP). The effects of three different pharmacological interventions on the cell cycle parameters have also been studied. Vascular smooth muscle cells isolated from SHRSP have significantly elevated G(2) + M phase of the cell cycle compared with cells from the normotensive reference strain, Wistar-Kyoto (WKY). This observation reflects an increased tetraploid and octaploid cell populations in vivo. Treatment with a combination of hydralazine and hydrochlorothiazide had no effect on the percentage of cells in G(2) + M phase of the cell cycle. Treatments with angiote nsin converting enzyme inhibitor, perindopril or AT(1) receptor antago nist, losartan, resulted in an equivalent blood pressure-lowering effe ct to that obtained with hydralazine/hydrochlorothiazide. In contrast to hydralazine/hydrochlorothiazide, these two treatments resulted in a highly significant regression of vascular smooth muscle polyploidy in the SHRSP. We hypothesise that angiotensin II plays an important role in cell cycle regulation in that, alone or in conjunction with one of the inhibitory proteins, it is able to stop the cell cycle progressio n after endoduplication but before the cytoplasmic division. Pharmacol ogical interventions which remove an excess of angiotensin II may allo w the cells to re-enter the cell cycle thus resulting in the regressio n of vascular smooth muscle polyploidy and improved arterial complianc e.