The renal medullary circulation and nitric oxide in hyperinsulinemic-hypertensive rats

Abstract

1. Insulin resistance may play a role in hypertensive patients. The renal medullary blood flow (MBF) is thought to be an important component of blood pressure and sodium balance. Nitric oxide (NO) activity within the renal medulla is the primary characterized factor in the maintenance of MBF and plays an important role in the pressure-natriuresis response. Because MBF, which is strongly influenced by the NO system, is thought to be an important component of blood pressure and sodium balance, we focused on MBF in hypertension being secondary in the development of insulin resistance. This study was designed to test the hypotheses that the MBF will be decreased and to determine the gene expression of three nitric oxide synthases (eNOS, nNOS, iNOS) in obese zucker rats (OZ). 2. 8–9 weeks male OZ and lean zucker rats (LZ) were divided into two group: Group1; OZ (n=7). Group2; LZ (n=7). Renal hemodynamic study; Each rat was instrumented with indwelling arterial and venous catheters. The tip of the arterial catheter was advanced to just below the level of left renal artery to permit continuous measurement of renal arterial pressure (RAP). For measurement of changes in renal cortical blood flow (CBF) and MBF in rats by laser-Doppler flowmetry, the optical fibers were implanted 2mm beneath the surface of the renal cortex to measure the net flux of red blood cells in the cortex and 6mm deep to monitor changes in the outer medulla. The RAP was adjusted from 160 to 80 mmHg with the use of balloon cuff. Gene expression study; We developed real-time RT-PCR that allows to absolutely quantify the gene expression of eNOS, nNOS, and iNOS in cortex and medulla of rat kidney using the standard curve and delta CT methods. 3. MAP was significantly increased in OZ. MBF was also significantly lower in OZ across a wide range of RAP without the significant change of CBF. The mRNA expression of eNOS and nNOS in renal medulla, which were significantly increased to a greater extent compared in renal cortex, were decreased in OZ compared in LZ. 4. MBF plays an important role in the development of hypertension in OZ. It seems reasonable to suppose that an impaired NO system could contribute to reduced MBF and sodium excretion, which would result in the development of hypertension in insulin resistance.