Angiotensin II is mitogenic in neonatal rat cardiac fibroblasts.

Abstract

muscle, effects on cardiac metabolism, and vasoconstriction of blood vessels.' In addition, clinical studies demonstrating the efficiency of angiotensin converting enzyme (ACE) inhibitors in the treatment of heart failure,2 myocardial ischemia,3 4and hypertension5.6 suggest that Ang II directly promotes pathological cell growth that participates in remodeling of the failing heart. Several animal studies have implicated Ang II in cardiac hypertrophy associated with hypertension; for instance, in a rat model of "pressure-overload" cardiac hypertrophy, treatment with an ACE inhibitor prevented the increase in left ventricular mass with no effect on afterload,7 suggesting that the growth effects of Ang II are direct. Moreover, chronic infusion of Ang II into rats increased left ventricular mass, even when the pressor activity of Ang II was blocked or a subpressor dose of Ang II was used.8 Recent experiments using cultured embryonic chick cardiomyocytes lend further support to the hypothesis that Ang II can directly produce cellular hypertrophy.9"10 It has not been established whether Ang II also has a direct growth effect on nonmyocyte cells of the heart, although recent studies suggest that cardiac fibroblasts are a target for Ang II; for instance, treatment with the ACE inhibitor captopril prevented myocardial fibrosis in a rat model with renovascular hypertension" and with induced myocardial infarction.12 In the latter study,

Angiotensin AT1 receptor antagonism and protection against cardiovascular end-organ damage

“…31 In neonatal rat cardiac fibroblast, angiotensin II stimulated the synthesis of protein, DNA and RNA, which was inhibited by EXP-3174, suggesting that angiotensin II-induced cardiac hypertrophy is, in part, secondary to stimulated increases in nonmyocyte cellular growth. 32 In cultured adult rat cardiac fibroblasts, angiotensin II stimulated the mRNA expression of collagen type I and III, the major fibrillar collagens in the heart, and decreased the mRNA of collagenase, the key enzyme for interstitial collagenase degradation. Losartan abolished the gene expression of collagen and had no effect on collagenase activity.…”

Functional role for the angiotensin II receptor (AT1A) 3′-untranslated region in determining cellular responses to agonist: evidence for recognition by RNA binding proteins

“…In j3h-UTR expressing cells, Ang II stimulated an intracellular calcium transient with a sustained phase, which mimics Ang II stimulated calcium transients in cells isolated from tissues expressing endogenous AT " receptors (e.g. vascular smooth muscle cells, adrenal zona glomerulosa cells and cardiac fibroblasts) [16,30,31]. In contrast, Ang II stimulation of k3h-UTR cells resulted in a more transient calcium response which returned to basal levels within 50 s. Together, these observations suggest that the 3h-UTR of the AT "A receptor has a role in cell signalling and growth, and that the cell is able to distinguish between the j3h-UTR and k3h-UTR transcripts.…”

Role of tissue angiotensin II in myocardial remodelling induced by mechanical stress

“…31 We have recently shown that unlike in cardiac myocytes, Ang II-induced MAP kinase activation is suppressed by tyrosine kinase inhibitors but is not affected by PKC downregulation in cardiac fibroblasts. 32 Ang II-induced MAP kinase activation was abolished by pretreatment with pertussis toxin and by overexpression of the G␤␥ subunit-binding domain of the ␤-adrenergic receptor kinase 1 in cardiac fibroblasts.…”