Superoxide dismustase mimetic tempol decreases blood pressure by increasing renal medullary blood flow in hyperinsulinemic-hypertensive rats.
Insulin resistance and compensatory hyperinsulinemia often coexist in hypertensive patients, which may play a role in the development of hypertension. Because medullary blood flow (MBF), which is strongly influenced by the nitric oxide (NO) system, is thought to be an important component of blood pressure and sodium balance, we focused particularly on MBF in fructose-induced hypertensive rats. Moreover, it has been reported that the increased reactive oxygen species (ROS) in the kidney may contribute to the development of hypertension. Our study was thus designed to test the hypotheses that MBF is diminished in fructose-hypertensive rats (FFR) and that administration of tempol, a membrane-permeable mimetic of superoxide dismutase (SOD), decreases mean arterial pressure (MAP) by increasing MBF. Male Sprague-Dawley rats (180 to 200 g) were divided into 6 groups: control untreated (C, n = 5), control tempol-treated (in drinking water) (CT, n = 4), control L-arginine-treated (in drinking water) (CA, n = 6), fructose-fed untreated (F, n = 7), fructose-fed tempol-treated (FT, n = 7), and fructose-fed L-arginine-treated rats (in drinking water) (FA, n = 6). MAP and 24-hour urine samples were measured weekly over a 4-week test period. Changes in MBF, cortical blood flow (CBF), and renal blood flow (RBF) were determined by implanted optical fiber-, laser- and pulse-Doppler flow measurement techniques 4 weeks after starting the diet. Fructose feeding resulted in hyperinsulinemia, significantly elevated MAP, decreased MBF without changes in RBF or CBF, and decreased sodium excretion in the F group compared to the C group. Administration of tempol significantly decreased MAP and plasma insulin in contrast to increased MBF and sodium excretion in the FT group compared to those in the F group. Results indicated that MBF played an important role in the development of hypertension in the F group. Impairment of renal medullary NO systems may induce sustained elevation of blood pressure and retention of sodium in fructose-fed rats. The decrease in MAP with an increase of MBF in the FT group is consistent with the hypothesis that tempol increases the level of NO available to influence mechanisms involved in the control of MBF.
Onuma
Shizuka
S
Second Department of Internal Medicine, Toho University School of Medicine, Ota-ku, Tokyo, Japan.
Nakanishi
Kazushige
K
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects*; D003497:Cyclic N-Oxides / Q000494:pharmacology* / Q000627:therapeutic use; D016166:Free Radical Scavengers / Q000494:pharmacology* / Q000627:therapeutic use; D005632:Fructose; D006946:Hyperinsulinism / Q000188:drug therapy / Q000503:physiopathology*; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D007328:Insulin / Q000097:blood; D007679:Kidney Medulla / Q000098:blood supply*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000652:urine; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000494:pharmacology*; D014563:Urodynamics / Q000187:drug effects
D001786:Blood Glucose; D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D007328:Insulin; D013113:Spin Labels; D005632:Fructose; D001120:Arginine; D012964:Sodium; D013482:Superoxide Dismutase; C001803:tempol