The present study tested the hypothesis that increasing epoxyeicosatrienoic acids by inhibition of soluble epoxide hydrolase (sEH) would lower blood pressure and ameliorate renal damage in salt-sensitive hypertension. Rats were infused with angiotensin fed a normal-salt diet or an 8% NaCl for 14 days. sEH inhibitor, 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), was given orally to angiotensin-infused animals during 14-day period. Plasma AUDA metabolite levels measured, they averaged...

Blockade of the renin-angiotensin system was studied in male Sprague-Dawley rats during long-term inhibition nitric oxide synthase. Nitro-L-arginine-methyl ester (L-NAME) placed drinking water for 4 weeks (approximately 100 mg/kg per day). Separate groups were coadministered angiotensin II antagonist A-81988 ranging from approximately 0.001 to 1 day. Control received only tap or alone. Each week, metabolic cages, and tail-cuff blood pressures samples taken. L-NAME produced a sustained...

Endothelin (ET) receptor blockade delays the progression of diabetic nephropathy; however, mechanism this protection is unknown. Therefore, aim study was to test hypothesis that ET(A) attenuates superoxide production and inflammation in kidney rats. Diabetes induced by streptozotocin (diabetic rats with partial insulin replacement maintain modest hyperglycemia [HG]), sham received vehicle treatments. Some also ETA antagonist ABT-627 (sham+ABT HG+ABT; 5 mg/kg per d; n = 8 10/group). During...

Recent evidence suggests that endothelin-1 (ET-1), perhaps through the ET B receptor, may participate in blood pressure regulation control of sodium excretion. Mean arterial (MAP) was continuously measured via telemetry implants male Sprague-Dawley rats. After 1 wk baseline measurements, rats were given either high (10%) or low (0.08%) NaCl chow for remainder experiment ( n = 5 each group). MAP significantly increased on a high-salt diet (115 ± 2 mmHg) compared with low-salt (103 mmHg; P...

Experiments were designed to test the hypothesis that elevated levels of endothelin 1 (ET-1) in vasculature activate NADPH oxidase and/or uncoupled nitric-oxide synthase (NOS), resulting \(\mathrm{O}_{2}^{{\bar{{\cdot}}}}\) production, and mediate increased constriction. Rat aortic rings incubated with ET-1 or vehicle presence absence superoxide dismutase (SOD), ebselen (glutathione peroxidase mimetic), apocynin (NADPH inhibitor), l-NAME (N^ω-nitro-l-arginine methyl ester) (NOS...

Endothelin-1 (ET-1) inhibits transport in various nephron segments, and the thick ascending limb of loop Henle (TALH) expresses ET-1 receptors. In many tissues, activation ET B receptors stimulates release NO, we recently reported that endogenous NO TALH chloride flux ( J Cl ). However, relationship between control has not been extensively studied. We hypothesized decreases NaCl by cortical TALHs through NO. Exogenous (1 nM) decreased from 118.3 ± 15.0 to 62.7 13.6 pmol · mm −1 min (48.3...

Experiments were designed to examine the role of endothelin (ET) receptors, specifically ETA in mediating renal vasoconstrictor effects ET-1 anesthetized Sprague-Dawley rats. Intravenous infusion at 25 pmol.kg-1 x min-1 for 60 min produced a significant increase mean arterial pressure (20 +/- 7%) and decreases plasma flow (-60 6%) glomerular filtration rate (-47 6%). Renal vascular resistance was significantly increased from 17 1 mmHg.ml-1 min.g kidney wt during control period 54 11...

Studies suggest that the inflammatory cytokine TNF-alpha plays a role in prognosis of end-stage renal diseases. We previously showed inhibition slowed progression hypertension and damage angiotensin II salt-sensitive hypertension. Thus, we hypothesize contributes to inflammation model mineralocorticoid-induced Four groups rats (n = 5 or 6) were studied for 3 wk with following treatments: 1) placebo, 2) placebo + inhibitor etanercept (1.25 mg.kg(-1).day(-1) sc), 3) deoxycorticosterone acetate...

Fructose feeding has been widely reported to cause hypertension in rats, as assessed indirectly by tail cuff plethysmography. Because there are potentially significant drawbacks associated with plethysmography, we determined whether blood pressure changes could be detected long-term monitoring telemetry age-matched male Sprague-Dawley rats fed either a normal or high-fructose diet for 8 weeks. Fasting plasma glucose (171±10 versus 120±10 mg/dL), insulin (1.8±0.5 0.7±0.1 μg/L), and...

Experiments were conducted to test the hypothesis that hypertension produced by chronic ET-1 infusion is mediated NADPH oxidase-dependent superoxide production. Mean arterial pressure (MAP) was continuously monitored in male Sprague Dawley rats telemetry. After baseline measurements, placed on a high-salt diet (8% NaCl) and osmotic minipumps implanted infuse (5 pmol/kg per minute intravenous) for 12 days. Control maintained only. Separate groups of also infused with given dismutase mimetic,...

Soluble epoxide hydrolase (sEH) inhibitors have been demonstrated to cardiovascular protective actions. This enzyme converts fatty acid epoxides their corresponding diols, and this conversion can alter the biologic activity of these metabolites. We hypothesized that 12-(3-adamantan-1-yl-ureido)dodecanoic (AUDA), a sEH inhibitor, would protect stroke-prone spontaneously hypertensive rats from cerebral ischemia. AUDA was administered 6-week-old male for 6 weeks, during which blood pressure...

Endothelin (ET) 1 is a potent vasoactive peptide implicated in the pathogenesis of hypertension and renal disease. The aim current study was to test hypotheses that ET-1 increases albumin permeability glomeruli isolated from normal rats chronic infusion will increase glomerular inflammation independent blood pressure. Glomerular determined change volume induced by exposing oncotic gradients. Incubation taken with at concentration did not produce direct contraction (1 nmol/L) significantly...

We hypothesized that the downregulation of Cyp2c by tumor necrosis factor (TNF) alpha contributes to hypertension and renal injury in salt-sensitive angiotensin hypertension. Male Sprague-Dawley rats were fed a high-salt diet (8% NaCl), osmotic minipumps implanted deliver II for 14 days. Rats divided into 3 groups: high salt, salt administered TNF-alpha blocker, etanercept. Arterial pressure increased from 94+/-5 148+/-7 mm Hg during week 1 group, whereas etanercept slowed blood elevation...

Growing evidence suggests that adverse childhood experiences (ACEs) increase the risks for coronary heart disease and hypertension in mid late adulthood. We previously reported early life stress induces a hyperreactive endothelin-dependent cardiovascular phenotype rat model. In present study, we evaluated whether exposure to ACEs is associated with greater peripheral resistance, arterial stiffness, blood pressure, or elevated circulating endothelin-1 levels humans. 221 healthy adolescents...

Selective endothelin A (ET_A) and combined ET_A ET_B receptor antagonists are being investigated for use in treating diabetic nephropathy. However, the receptor-specific mechanisms responsible producing potential benefits have not been discerned. Thus, we determined actions of receptors on measures glomerular function renal inflammation early stages injury rats through selective antagonists. Six weeks after streptozotocin (STZ)-induced hyperglycemia, were given...