Functional cross-talk between the cyclic AMP and Jak/STAT signaling pathways in vascular smooth muscle cells

Angiotensin II (Ang II), the primary effector of the renin-angiotensin syst em, is a multifunctional hormone that plays an important role in vascular f unction. In addition to its classical vasoconstrictor action, more recent s tudies demonstrated that Ang II stimulates the growth of a number of cell t ypes, including vascular smooth muscle cells (SMC) (reviewed in [1-3]). In vivo studies have shown that chronic infusion of Ang II leads to the develo pment of vascular hypertrophy in rats, whereas administration of angiotensi n-converting enzyme (ACE) inhibitors or Ang II receptor antagonists prevent s or regresses vascular hypertrophy in models of genetic and experimental h ypertension [4]. Consistent with in vivo data, several laboratories have sh own that Ang II stimulates protein synthesis and induces cellular hypertrop hy, but not cell proliferation, in cultured aortic SMC [5-9]. Ang II also i nduces directed migration (chemotaxis) of vascular SMC [10, 11], although i ts effect is less prominent than that of platelet-derived growth factor (PD GF). The cellular mechanisms underlying these diverse actions of Ang II are not clearly understood but are likely to involve the activation of distinc t signaling pathways.