Studies of hypertension-induced vascular hypertrophy in cultured smooth muscle cells from spontaneously hypertensive rats.

Abstract

SUMMARY Mechanisms of vascular hypertrophy induced by hypertension were studied in cultured aortic smooth muscle cells from spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP) and compared with those from normotensive Wistar-Kyoto (WKY) rats. Fetal calf serumstimulated ornithine decarboxylase (ODC) activity of cultured smooth muscle cells was greater in SHR and SHRSP than in WKY. Beta-but not alpha-adrenergic agonist stimulated ODC activity acutely in cultured smooth muscle cells from WKY, and isoprenaline-induced activation was blocked by the beta-blocker, propranolol, and enhanced by the phosphodiesterase inhibitor, l-methyl-3-isobutylxanthine. These results indicate that cultured vascular smooth muscle cells from SHR and SHRSP are more prone to increase the protein synthesis than those from WKY through the trophic induction of ODC activity and that the regulation of ODC activity by catecholamines is mediated through betaagonistic effect in cultured smooth muscle cells. (Hypertension 5: 887-892, 1983) KEY WORDS • catecholamine * cultured vascular smooth muscle cells ornithine decarboxylase * stroke-prone spontaneously hypertensive rats spontaneous hypertension I T is now established that functional as well as structural vascular changes are important in the pathogenesis of genetic hypertension. Medial hypertrophy of arterial walls is generally regarded as being secondary to blood pressure rise but involved in the further development and maintenance of hypertension.' However, in spontaneously hypertensive rats (SHR), the thickening of the arterial walls is induced at the early stage or prehypertensive stage of hypertension. "7 Furthermore, we found that vascular noncollagen and collagen protein synthesis was enhanced not only by the blood pressure rise itself but also by genetic predisposition and neural activation, 8 and that vascular hypertrophy in SHR was prevented by the prolonged treatment of a low dose of beta-blocker which did not obviously affect blood pressure. 9Under tissue culture condition free from the influence of blood pressure, smooth muscle cells from SHR and stroke-prone SHR (SHRSP) grew faster than those from normotensive Wistar-Kyoto (WKY) rats, and la-

Spontaneously hypertensive rat vascular smooth muscle cells in culture exhibit increased growth and Na+/H+ exchange.

“…Our findings on VSMC growth are similar to those of Yamori and colleagues (15,16) (Table I, top section) that was not associated with a decrease in cell number at confluence (Table I, bottom section). This decrease likely reflects a prolongation in SHR VSMC doubling time over serial passages, although selective loss of a population of more rapidly dividing cells cannot be excluded.…”

“…In either instance, abnormal cell growth must be present. Yamori and colleagues (15,16) demonstrated that VSMC cultured from aortae of 12-and 24-wk SHR and SHR stroke-prone rats proliferated significantly more rapidly than those from agematched Wistar Kyoto (WKY) rats. These investigators also observed that SHR VSMC maintained increased DNA synthesis at any concentration of extracellular Na' ( 15).…”

Enhanced DNA synthesis in heart and kidney of newborn spontaneously hypertensive rats.

“…A growth abnormality in the aorta of SHR has already been suggested based on observations of higher ornithine decarboxylase activity in cultured aortic smooth muscle cells from SHR when compared with that in WKY. 18 It is not clear whether the observed increase of DNA synthesis for heart and kidney from SHR is a consequence of an intrinsic genetic growth abnormality 19 or due to circulating growth blood factors present in SHR. The concept of circulating growth factors receives support from the demonstration that crosscirculating WKY and SHR results in medial smooth muscle thickening and hypertrophy of the portal veins obtained from the WKY, 20 and also from the development of sustained high blood pressure in genetically normotensive Sprague-Dawley newboms nursed by spontaneously hypertensive foster mothers.…”

Vasodilators inhibit acute alpha 1-adrenergic receptor-induced trophic responses in the vasculature.

“…10 Elevated levels of ODC activity, a well-established obligatory biochemical event that occurs early in the process of tissue hypertrophy, is characteristic of all tissues undergoing rapid growth processes. 11 ODC is the rate-limiting enzyme in the formation of polyamines, which are important intracellular regulators of DNA, RNA, and protein synthesis during cellular prolifera-tion and growth.…”