Influence of blood pressure on development of aortic medial smooth muscle hypertrophy in spontaneously hypertensive rats.

Abstract

The hypothesis that a primary stimulus for aortic medial hypertrophy in spontaneously hypertensive rats (SHR) is increased blood pressure was tested by determining whether development of smooth muscle cell hypertrophy and hyperploidy in SHR could be dissociated from blood pressure levels in rats treated with various antihypertensive drugs with different mechanisms of action. Wistar-Kyoto rats (WKY) and SHR were treated between 2 and 5 months of age with captopril (375 mg/L), hydralazine (40 mg/L), or propranolol (1.5 mg/L) administered in their drinking water. Smooth muscle hypertrophy and hyperploidy were analyzed by morphometric evaluation of medial smooth muscle content, flow cytometric analysis of the frequency of polyploid smooth muscle cells, and biochemical estimates of smooth muscle cell number. All drugs significantly lowered blood pressure in SHR compared with untreated controls (order of efficacy: captopril greater than hydralazine greater than propranolol). Captopril also was most effective at changing blood pressure in WKY, while propranolol and hydralazine had similar blood pressure-lowering effects. The efficacy of drugs in preventing the development of smooth muscle cell polyploidism and medial hypertrophy in SHR was the same as their efficacy in lowering blood pressure, although propranolol had no effect on medial smooth muscle hypertrophy despite lowering blood pressure by 26 mm Hg. Regression analyses showed a high degree of correlation between blood pressure and the frequency of polyploid smooth muscle cells and medial smooth muscle content. These results are consistent with the hypothesis that aortic medial hypertrophy may be, in part, a response to increased blood pressure or wall stress. However, analysis of covariance and two-stage multiple regression analyses indicated that captopril had an effect over and above that predicted by its blood pressure-lowering effect. Furthermore, propranolol lowered blood pressure but did not affect medial hypertrophy. These results suggest that smooth muscle hypertrophy is not simply a response to increased blood pressure, but that other factors, such as angiotensin II, may be important in modulating aortic medial hypertrophy in SHR.

Role of adrenergic receptors in vascular remodelling of the rat choroid

“…In normotensive rats, propranolol produces only small e ects on blood pressure, which remain in the normal range (Owens, 1987). Similarly, using laser Doppler¯owmetry to measure blood¯ow in the posterior choroid and vortex veins, we were unable to detect any apparent change after acute intravenous administration of propranolol (Steinle & Smith, unpublished).…”

Angiotensin II induces c-fos expression in smooth muscle via transcriptional control.

“…29 For example, the plasma renin level is normal in the spontaneously hypertensive rat, yet captopril reduces vascular hypertrophy. 5 Recently, all of the components of the renin-angiotensin system have been demonstrated in the vessel wall, 29 - 30 and in some experimental models of hypertension (e.g., the spontaneously hypertensive rat and the chronic two-kidney, one clip hypertensive model) there is evidence to suggest that this local tissue renin-angiotensin system is elevated in hypertension. 31 - 32 This raises the possibility that an autocrine or paracrine system exists, which may be activated in hypertension.…”

“…One important mediator may be the vasoactive peptide angiotensin II (Ang II). Owens 5 reported that treatment of the spontaneously hypertensive rat with the angiotensin converting enzyme inhibitor captopril resulted in a reduction in aortic hypertrophy. This effect may be due, in part, to the blockade of Ang II production since captopril produced a greater reduction in thoracic aortic smooth muscle mass than the nonspecific vasodilator hydralazine, despite equal reduction in blood pressure.…”

Long-term low-dose angiotensin converting enzyme inhibitor treatment increases vascular cyclic guanosine 3',5'-monophosphate.

“…- 23 Therefore, a reduced contractility of the aortic wall in response to norepinephrine could be due to a reduced smooth muscle mass after long-term ACE inhibitor treatment.…”