November 1, 1990Open Access
Atrial natriuretic polypeptide inhibits hypertrophy of vascular smooth muscle cells.
Structured PICO
Does atrial natriuretic polypeptide inhibit hypertrophy and proliferation in cultured rat aortic smooth muscle cells?
P
Population
Cultured rat aortic smooth muscle (RASM) cells
I
Intervention
Atrial natriuretic polypeptide (alpha-rat ANP [1-28]) at 10(-7) M and 10(-6) M
C
Comparator
Control conditions (basal, or stimulated with angiotensin II or transforming growth factor-beta without ANP)
O
Outcome
Cell growth characteristics including proliferation (3H-thymidine incorporation, cell number) and hypertrophy (3H-uridine and leucine incorporation, RNA and protein syntheses, cell size)surrogate
ANP exerts antihypertrophic and antimitogenic effects on vascular smooth muscle cells via guanylate cyclase-linked receptors, which may serve as a compensatory mechanism in hypertension.
Abstract
Vascular remodeling is central to the pathophysiology of hypertension and atherosclerosis. Recent evidence suggests that vasoconstrictive substances, such as angiotensin II (AII), may function as a vascular smooth muscle growth promoting substance. To explore the role of the counterregulatory hormone, atrial natriuretic polypeptide (ANP) in this process, we examined the effect of ANP (alpha-rat ANP 1-28) on the growth characteristics of cultured rat aortic smooth muscle (RASM) cells. ANP (10(-7) M) significantly suppressed the proliferative effect of 1% and 5% serum as measured by 3H-thymidine incorporation and cell number, confirming ANP as an antimitogenic factor. In quiescent RASM cells, ANP (10(-7), 10(-6) M) significantly suppressed the basal incorporations of 3H-uridine and leucine by 50 and 30%, respectively. ANP (10(-7), 10(-6) M) also suppressed AII-induced RNA and protein syntheses (by 30-40%) with the concomitant reduction of the cell size. Furthermore, ANP also significantly attenuated the increase of 3H-uridine and leucine incorporations caused by transforming growth factor-beta (4 x 10(-11), 4 x 10(-10) M), a potent hypertrophic factor. These results indicate that ANP possesses an antihypertrophic action on vascular smooth muscle cells. Down-regulation of protein kinase C by 24-h treatment with phorbol 12,13-dibutyrate did not inhibit ANP-induced suppression on 3H-uridine incorporation. Based on the observation that ANP was more potent than a ring-deleted analogue of ANP on inhibiting 3H-uridine incorporation, we conclude that the ANP's inhibitory effect is primarily mediated via the activation of a guanylate cyclase-linked ANP receptor(s). Indeed 8-bromo cGMP mimicked the antihypertrophic action of ANP. Accordingly, we speculate that in addition to its vasorelaxant and natriuretic effects, the antihypertrophic action of ANP observed in the present study may serve as an additional compensatory mechanism of ANP in hypertension.