Antihypertensive role of kidney: Focus on tissue kallikreins

Abstract

Regulation of blood pressure (BP) depends mostly on genetic and environmentalfactors. Among different physiological mechanisms responsible for a discernibleincrease in BP (hypertension), two major mechanisms are important: (a) matrixremodeling associated with arterial wall thickening with apparent reduction inblood flow and (b) activation of renin-angiotensin system (RAS). To counteractthe BP rise beyond physiological limit and to ameliorate BP-rise-associatedcomplications, nature has designed an important endogenous regulatorymechanism operative especially in kidney, the kallikrein-kinin system (KKS).In cortical collecting duct of the kidney, KKS plays a significant role in BPregulation under salt excess condition. This protective phenomenon potentiallyacts as a hypotensive mechanism to regulate abnormal BP increase. Thefunctional components of the KKS are the kallikrein, a serine protease, andkinin. Proteolytic action of kallikrein on precursor kininogen forms vasoactivepeptide kinin by enzymatic cleavage. Upon release, kinin binds to the B2receptor on cell surface and exerts antihypertensive effect. Though KKS operatesin both cardiovascular and renal systems, for the sake of simplicity and to have afocused but detailed understanding, only the regulatory mechanisms of renalKKS on BP homeostasis has been considered for discussion in this review.