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Vascular smooth muscle polyploidy in the development and regression of hypertension
Abstract:
1. Two groups of spontaneously hypertensive rats (SHR) were treated with enalapril (25-30 mg/kg per day): Group I received treatment from 4 to 14 weeks of age to inhibit development of hypertension and Group R received the drug from 14 to 20 weeks of age to reverse established hypertension. 2. Systolic blood pressure, ploidy of aortic smooth muscle cells (flow cytometric DNA analysis) and aortic hypertrophy (medial cross-sectional area) were determined at times both during and after enalapril treatment (up to 30 weeks). 3. Enalapril treatment normalized blood pressure to that of age-matched Wistar-Kyoto rats in both groups. Blood pressure rose again following cessation of treatment. 4. In untreated SHR the incidence of polyploid cells increased concomitantly with increasing pressure throughout the time studied, whereas in Group I the incidence remained low. In Group R, the incidence of polyploidy directly paralleled both the decrease (normalization) and the rise in blood pressure following cessation of treatment. 5. Hence, the incidence of vascular smooth muscle cell polyploidy is not simply a result of growth of the vessel with increasing age of the SHR, but parallels inhibition, reversal, and redevelopment of hypertension.
Insights
Enalapril normalized blood pressure in spontaneously hypertensive rats (SHR). Vascular smooth muscle cell polyploidy paralleled blood pressure changes, indicating it is linked to hypertension development and reversal, not just aging.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Cell Biology
Background:
- Spontaneously hypertensive rats (SHR) exhibit elevated blood pressure and associated vascular changes.
- Vascular smooth muscle cell (VSMC) polyploidy has been observed in hypertension, but its direct relationship to disease progression and treatment is unclear.
Purpose of the Study:
- To investigate the effect of enalapril on blood pressure and VSMC polyploidy in SHR.
- To determine if VSMC polyploidy is a cause or consequence of hypertension in SHR.
Main Methods:
- Two groups of SHR were treated with enalapril: one to inhibit hypertension development (Group I) and another to reverse established hypertension (Group R).
- Systolic blood pressure, VSMC ploidy (flow cytometry), and aortic hypertrophy were measured during and after enalapril treatment.
- Measurements were compared to age-matched Wistar-Kyoto rats.
Main Results:
- Enalapril normalized blood pressure in both treatment groups, which returned to hypertensive levels upon drug cessation.
- In untreated SHR, polyploidy increased with blood pressure.
- In enalapril-treated groups, VSMC polyploidy levels paralleled blood pressure changes, decreasing with treatment and increasing after cessation.
Conclusions:
- Enalapril effectively controls blood pressure in SHR, both preventing its rise and reversing established hypertension.
- Vascular smooth muscle cell polyploidy in SHR is directly associated with the state of hypertension, reflecting its inhibition, reversal, and redevelopment.
- VSMC polyploidy is a dynamic marker that parallels the course of hypertension, rather than a simple consequence of vascular growth with age.