ROLE OF ENDOTHELIN IN MEDIATING THE ATTENUATED RENAL HEMODYNAMICS IN DAHL SALT-SENSITIVE HYPERTENSION

The aim of this study was to evaluate the role of endothelin (ET) in t he hypertension associated with giving a high sodium diet in Dahl salt -sensitive (DS) rats. To achieve this goal, we examined the effects of intravenous infusion of the nonspecific ETA-ETB antagonist on arteria l pressure and renal function in conscious, chronically instrumented D S and Dahl salt-resistant (DR) rats. After 3 weeks on a high sodium (8 %) diet, mean arterial pressure (MAP) in DS rats (166+/-3 mm Hg) was s ignificantly higher than in DR rats (124+/-3 mm Hg). Baseline glomerul ar filtration rate (GFR) and renal plasma flow (RPF) in DS rats (1.92/-0.25 mL/min and 7.07+/-0.80 mL/min) were lower than in DR rats (2.52 +/-0.21 mL/min and 7.98+/-0.85 mL/min), respectively. Renal vascular r esistance was significantly higher in DS rats (32.78+/-5.88 mm Hg.mL(- 1).min(-1)) than in DR rats (24.60+/-5.04 mm Hg.mL(-1).min(-1)). Intra venous infusion of the ET antagonist SE 209670 at a dose of 30 mu g.kg (-1).min(-1) for 75 minutes caused a significant decrease in MAP in DS rats (from 166+/-3 to 144+/-4 mm Hg). In contrast, the effect of the ET antagonism on MAP in DR rats was not significant. ET-antagonist inf usion tended to improve GFR and RPF in DS but not in DR rats. To deter mine the renal effects of ET antagonism independent of the systemic he modynamic responses, we examined the effects of the same ET antagonist in rats chronically implanted with a renal interstitial catheter. Art erial pressure in DS rats (181+/-5 mm Hg) was significantly higher tha n in DR rats (135+/-3 mm Hg). Renal interstitial infusion of SE 209670 at a dose of 200 ng.kg(-1).min(-1) for 60 minutes caused no change in MAP in DS or DR rats. Intrarenal ET antagonism significantly increase d GFR (25%), RPF (30%), urine how (32%), and urinary sodium excretion (25%) in DS rats, while it had no significant effect in DR rats. Fract ional excretion of sodium was not significantly changed by renal inter stitial infusion of the ET antagonist in DS rats, indicating that impr oved renal excretory function in DS rats is most likely due to the ass ociated improvement in renal hemodynamics. We conclude that ET may pla y a role in the attenuated renal hemodynamics and possibly the develop ment of Dahl salt-sensitive hypertension.