Angiotensin II induces smooth muscle cell proliferation in the normal and injured rat arterial wall.

Abstract

The present study was undertaken to explore the possibility that neointimal smooth muscle cells, the characteristic cells of restenosis and atherosclerosis, are selectively stimulated to replicate by a hypertensive stimulus. Angiotensin II (AII) was infused by osmotic minipumps for 2 weeks in 4.5-month-old rats. Group A received AII (200 ng/min) 2 weeks after a balloon catheter-induced injury of the thoracic aorta and left common carotid artery. Group B received only AII, group C only balloon denudation, and group D neither balloon injury nor AII. During the AII or Ringer's solution infusion, all animals received [3H]thymidine via a second minipump to measure DNA synthesis. AII increased the systolic pressure by more than 40 mm Hg. AII significantly increased DNA synthesis in the media of the carotid artery from 0.2 +/- 0.2% in group C to 2.5 +/- 1.5% in group A (mean +/- SD, n = 5 or 6). DNA synthesis in the neointima of the carotid artery significantly increased with AII from 4.8 +/- 4.2% in group C to 19.8 +/- 13.9% in group A. Cross-sectional area of the neointima almost doubled during AII infusion, and it increased approximately 25% in the media. Comparable results were obtained in the aorta. In a second experiment, AII was infused (125 ng/min) for 2 weeks in 11-week-old rats. Concomitantly, [3H]thymidine was given. Control rats received Ringer's solution and [3H]thymidine in their pumps. Blood pressures were elevated to the same extent as in the older animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Molecular and cellular mechanisms of action of angiotensin II (AT1) receptors in vascular smooth muscle

“…In vivo AII has been shown to induce smooth muscle proliferation measured by incorporation of bromodeoxyuridine in the balloon injured rat carotid artery. 61 In a later study using the same model the effect of AII was shown to be more marked on neointimal cells and that medial proliferation in response to AII was transient in uninjured regions of the vessel compared with the sustained mitogenic action of AII on the neointima. 62 The growth promoting effect of AII on neointimal cells has been reported to be independent of sympathetic activation.…”

Aspects of gene polymorphisms in cardiovascular disease: the renin‐angiotensin system

“…The growth-promoting effects of Ang II are modulated, under normal conditions, by endothelium-derived factors. Removal of the endothelium, for example by balloon injury, may alter the vascular structure and promote the development of intimal hyperplasia, and this may be reverted by ACE inhibition in experimental animal models [17,18].…”

“…Dzau et al have indeed suggested a prominent role of the RAS system in the pathogenesis of restenosis, demonstrating that Ang II can modulate smooth muscle cell growth in vitro [20]. In vivo studies have reported that Ang II infusion induces marked intimal smooth muscle cell proliferation in rat carotid arteries [17,21], and that ACE inhibitors suppress myointimal proliferation after vascular injury [14,18]. Intimal thickening can also be prevented by Ang II receptor type-1 antagonists [66].…”

Receptors and their classification: focus on angiotensin II and the AT2 receptor

“…Ang II has also been implicated in cardiovascular and renal pathology, such as cardiac left ventricular hypertrophy, neointima formation, post infarct remodelling and nephrosclerosis. [4][5][6] Ang II is capable of inducing cell proliferation and is as such probably contributing under pathological conditions to structural alterations in various organs. [6][7][8] Ang II mediates its actions through a set of angiotensin receptors (Table 1).…”

“…[4][5][6] Ang II is capable of inducing cell proliferation and is as such probably contributing under pathological conditions to structural alterations in various organs. [6][7][8] Ang II mediates its actions through a set of angiotensin receptors (Table 1). 9 In the past, both the short and long-term effects of Ang II were thought to be mediated by a single receptor.…”