Blunted norepinephrine natriuresis in the isolated spontaneously hypertensive rat kidney

In order to characterize the relationship between blood pressure and renal sodium handling in the Kyoto spontaneously hypertensive rat (SHR), we did renal clearance and isolated perfusion studies in SHR and Wistar-Kyoto controls (WKY). Clearance studies revealed no differences in renal function between SHR and WKY. Isolated perfused kidneys from SHR demonstrated a diminished glomerular filtration rate (GFR) compared to WKY kidneys when both were perfused at normotensive pressures. Increasing the perfusion pressures to hypertensive levels by adjusting the perfusate flow rate increased both the GFR and sodium excretion to equivalent values. However, the addition of norepinephrine 15 ng/ml, to the perfusate resulted in a far greater natriuretic response in WKY kidneys than in SHR, despite equivalent increases in perfusion pressures, renal resistances, GFR, and filtration fractions. These results suggest that norepinephrine exerts a direct or indirect inhibitory action on renal sodium transport, and this effect is diminished in SHR kidneys. Additionally, abnormalities in renal sodium transport may play a role in the pathogenesis of hypertension in the SHR.