Telmisartan improves endothelial dysfunction and renal autoregulation in Dahl salt-sensitive rats.
Hypertensive vascular disorders are characterized by endothelial dysfunction. Loss of renal autoregulation causes glomerular hypertension. However, the relationship between the autoregulatory response and glomerular damage has not been well examined. We examined the contributions of uncoupled endothelial nitric oxide synthase (eNOS) in hypertensive renal disease, and the relationship between the degree of autoregulation impairment and glomerular injury. We also investigated the effects of telmisartan on eNOS coupling and renal autoregulation. Male Dahl salt-sensitive hypertensive (DS) rats (14-week old) fed an 8% salt diet were used to examine endothelial dysfunction and impaired renal autoregulation caused by glomerular hypertension. Some DS rats were treated with telmisartan (3.0 mg kg(-1) day(-1)), an angiotensin receptor blocker, for 2 weeks. Increased superoxide production and decreased nitric oxide production, as detected by fluorescent indicator perfusion methods, were observed in the glomeruli and arterioles of hypertensive DS rats. Telmisartan improved the imbalance of superoxide and nitric oxide in the glomeruli and arterioles. Decreased serum tetrahydrobiopterin levels and coupled eNOS seen in the DS rat kidney were improved with telmisartan treatment. The endothelial relaxation reaction was impaired in DS rat aortic arteries. Autoregulatory capacity in response to step changes in perfusion pressure was also impaired in DS rat kidney. Treatment with telmisartan improved these abnormalities. Endothelial dysfunction in the glomeruli and impaired renal autoregulation, which may cause glomerular sclerosis, were observed in DS rat kidney. Telmisartan treatment improves these dysfunctions in hypertensive renal disease.
Satoh
Minoru
M
Division of Nephrology, Department of Internal Medicine, Kawasaki Medical School, Kurashiki, Okayama, Japan. msatoh@med.kawasaki-m.ac.jp
Haruna
Yoshisuke
Y
Fujimoto
Sohachi
S
Sasaki
Tamaki
T
Kashihara
Naoki
N
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D001708:Biopterins / Q000031:analogs & derivatives / Q000096:biosynthesis; D015153:Blotting, Western; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D006706:Homeostasis; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000378:metabolism; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000032:analysis; D051381:Rats; D020303:Rats, Inbred Dahl; D017382:Reactive Oxygen Species / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000235:genetics; D000077333:Telmisartan
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D017382:Reactive Oxygen Species; D018048:Receptors, Purinergic P2; D001708:Biopterins; D052250:Nitric Oxide Synthase Type III; C003402:sapropterin; D000077333:Telmisartan