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 G2 + M phase of the cell cycle 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 G2 + 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 G2 + M phase of the cell cycle. Treatments with angiotensin converting enzyme inhibitor, perindopril or AT1 receptor antagonist, losartan, resulted in an equivalent blood pressure-lowering effect 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 progression after endoduplication but before the cytoplasmic division. Pharmacological interventions which remove an excess of angiotensin II may allow the cells to re-enter the cell cycle thus resulting in the regression of vascular smooth muscle polyploidy and improved arterial compliance.
D000804:Angiotensin II / Q000502:physiology*; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D002453:Cell Cycle; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan; D008955:Models, Cardiovascular; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D011003:Ploidies; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D019808:Losartan