Actions of angiotensin II on the renal microvasculature

Angiotensin II (AngII) exerts powerful effects on the renal microcirculatio n to influence a variety of functions. This review summarizes some of the m ajor findings over the past 10 years as they elucidate the multiple roles t hat AngII plays in the regulation of whole kidney blood flow, perfusion of cortical and medullary regions, and renal autoregulation. Topics of discuss ion include localization of AngII receptor types and subtypes in the renal vasculature, action of AngII on vascular smooth muscle cells of the afferen t and efferent arterioles, and intracellular signaling pathways. Within the microvasculature, AngII causes potent constriction in both the efferent an d efferent arterioles, with responses modulated by paracrine and autocrine factors of endothelial and macula densa origins. With regard to renal autor egulatory mechanisms consisting of the myogenic response and the tubuloglom erular feedback mechanism, the myogenic response appears to operate indepen dent of the renin-angiotensin system. On the other hand, tubuloglomerular f eedback activity is often directly proportional to concentrations of AngII, especially in high renin states. Of the two types defined to date, the AT( 1) is the predominant receptor in the adult rat kidney mediating the vascul ar effects of AngII. AT(2) receptor is highly expressed in the fetal kidney and is important for renal development, but is very weakly expressed in ad ult animals. Nevertheless, AT(2) receptors may mediate vasodilation under c ertain conditions. The signaling transduction pathways for AT(1) receptors include Gq/11-protein and protein kinase C activation. AngII causes constri ction of the afferent arteriole primarily by stimulation of calcium entry v ia voltage-sensitive, L-type channels, whereas AngII effects on the efferen t arteriole are due to calcium release from intracellular stores and calciu m entry through voltage-independent calcium entry channels. Future experime nts should contribute to a more in-depth understanding of the modulation of AngII effects by other vasoactive agents and interactions between differen t second-messenger signaling pathways in health and disease.