Effect of Nitric Oxide Synthase Inhibition on Renal Circulation and Excretory Function in Anaesthetized Rats

Abstract

The effects of nitric oxide synthase (NOS) inhibition (effected using L-NAME, 14 mg (kg body mass (BM))(-1), administered intravenously) on systemic and renal circulation and renal excretory function has been investigated in anaesthetized Wistar rats subjected to one of two different degrees of isotonic extracellular (EC) volume expansion (40 and 60 ml x kg(-1) (240 min)(-1)). The administration of L-NAME resulted in an increase in mean arterial blood pressure and total peripheral vascular resistance (TPR), and a significant reduction in cardiac output (CO) and the kidney fraction of CO in both experimental groups. The total renal blood flow (RBF) dropped from 557 + 43.4 to 149 +/- 13.1 ml x min(-1) (100 g BM)(-1) and from 592 +/- 45.9 to 191 +/- 16.3 ml x min(-1) (100 g BM)(-1) in the 40 and 60 ml x kg(-1) (240 min)(-1) experimental volume expansion groups, respectively. A redistribution of the intrarenal circulation from the medulla of the kidney toward the cortex may have occurred. The NOS inhibition induced a significant decrease in the glomerular filtration rate (GFR; from 1.18 +/- 0.10 to 0.53 +/- 0.08 ml x min(-1) (100 g BM)(-1) and from 1.26 +/- 0.07 to 0.73 +/- 0.08 ml x min(-1) (100 g BM)(-1) in the 40 and 60 ml x kg(-1) (240 min)(-1) experimental volume expansion groups, respectively), and the filtration fraction increased. The urine excretion dropped in parallel with the GFR, while the reduction in sodium and potassium excretion was more marked than that of the GFR, raising the possibility of a direct effect on the kidney tubules. The difference in EC volume expansion (the calculated increases in the EC volume in the last 90 min were 1.30 and 5.44% in the two time control groups and 3.66 and 7.45% in the two L-NAME-treated groups) did not induce any significant modification of the L-NAME effect.

Pharmacological evidence that 5‐HT1D activation induces renal vasodilation by NO pathway in rats

“…There have been several reports demonstrating decreased renal blood flow, increased renal vascular resistance and elevated SBP after treatment with nonselective NOS inhibitors in rats. 40,41 Our results are according to these statements, since, in the presence of L-NAME, the administration of a NOS substrate, L-arginine, was able to return to baseline values of haemodynamic variables (see Table 1).…”

Modulation of Renal Blood Flow and Vascular Tone by Neuronal Nitric Oxide Synthase-Derived Nitric Oxide

“…There have been a number of reports demonstrating decreased renal blood flow, increased renal vascular resistance and elevated systemic blood pressure after treatment with nonselective NOS inhibitors in anesthetized and conscious rats [38,39,40,41]. Impairment of NO production via eNOS blockade is involved in these hemodynamic changes; however, the role of NO derived from nNOS in the control of the renal circulation has not been determined.…”

Nitric oxide and AQP2 in hypothyroid rats: A link between aging and water homeostasis

“…In this sense, several authors have shown that impaired urinary diluting capacity would be associated with an upregulation of arginine vasopressin (AVP)-mediated AQP2 expression and membrane trafficking in the inner medulla in the hypothyroid state [9][10][11][12]. On the other hand, studies conducted in both humans and experimental animals demonstrate that NO decreases renal vascular resistance and increases GFR, natriuresis and water excretion [13,14]. It is well known that AVP increases collecting duct water permeability by enhancing AQP2 channel insertion in the apical membrane of principal cells through the AVP/cAMP pathway [14].…”