Nitric Oxide in Hypertension: Relationship With Renal Injury and Left Ventricular Hypertrophy

Hypertension IS accompanied by architectural changes m the kidney, heart, and vessels that are often maladaptlve and can eventually contribute to end-organ disease such as renal failure, heart failure, and coronary disease Nitric oxide, an endogenous vasodllator and antlthrombotlc agent synthesized m the endothehum by a constltutlve mtnc oxide synthase, mhlblts growth-related responses to injury m vascular cells Specifically, m the presence of hypertension, mtrlc oxide may work m the kidney by mhlbltmg both mesangal cell hypertrophy and hyperplasla as well as synthesis of extracellular matrix and m the heart and systemic vessels by modulatmg smooth muscle cell hypertrophy and hyperplasla The effects of mtnc oxide are antagomstlc of the effects of anglotensm II Shear stress and cychc strain, physlcal forces known to operate m hypertension, are accompanied by mcreases m endothehal mtrlc oxide synthase expression, nitric oxide synthase protein, and mtrlc oxide synthase activity m endothehal cells Experimental studies using genetic models of hypertension show a variation m hypertension-modulated vascular nitric oxide synthase activity m different strains of rats These studies suggest that upregulatlon of vascular nitric oxide synthase activity 1s a homeostatlc adaptation to mcreased hemodynamlc workload m hypertension and that this may help prevent end-organ damage. If these findings apply to humans, differences m end-organ disease seen m patients with slmllar degrees of hypertension may be due m part to genetic differences m vascular mtrlc oxide synthase activity m response to hypertension (Hypertension. 1998;31[part 2]:189-193.)