UP-REGULATION OF RENAL AND VASCULAR NITRIC-OXIDE SYNTHASE IN YOUNG SPONTANEOUSLY HYPERTENSIVE RATS

The available data on the role of the L-arginine/nitric oxide (NO) pat hway in the genesis of hypertension in spontaneously hypertensive rats (SHR) are limited and contradictory. In an attempt to address this is sue, male SHR were studied during the early phase of evolution of hype rtension (age 8 to 12 weeks) to distinguish the primary changes of NO metabolism from those caused by advanced hypertension, vasculopathy, a nd aging late in the course of the disease. A group of age-matched mal e Wistar-Kyoto rats (WKY) served as controls. The SHR exhibited a mark ed rise in arterial blood pressure and a significant increase in urina ry excretion and plasma concentration of NO metabolites (nitrite/nitra te [NOx]). Likewise, the SHR showed a significant elevation of thoraci c aorta NO synthase (NOS) activity coupled with significant increases of kidney, aorta, inducible NOS (iNOS), and endothelial NOS (eNOS) pro teins. In an attempt to determine whether the enhanced L-arginine/NO p athway is a consequence of hypertension, studies were repeated using 3 -week-old animals before the onset of hypertension. The study revealed significant increases in urinary NOx excretion as well as vascular eN OS and renal iNOS proteins. In conclusion, the L-arginine/NO pathway i s upregulated in young SHR both before and after the onset of hyperten sion. Thus, development of hypertension is not due to a primary impair ment of NO production in SHR. On the contrary, NO production is increa sed in young SHR both before and after the onset of hypertension.