OBJECTIVE: The present study was performed to examine whether the blood pressure (BP)-lowering effects of soluble epoxide hydrolase (sEH) inhibition in two-kidney, one-clip (2K1C) Goldblatt hypertension are nitric oxide (NO) dependent. METHODS: Mice lacking the endothelial NO synthase (eNOS) gene (eNOS-/-) and their wild-type controls (eNOS+/+) underwent clipping of one renal artery. BP was monitored by radiotelemetry and the treatment with the sEH inhibitor cis-4-[4-(3-adamantan-1-yl-ureido)cyclohex-yloxy]-benzoic acid (c-AUCB) was initiated on day 25 after clipping and lasted for 14 days. Renal concentrations of epoxyeicosatrienoic acids (EETs) and their inactive metabolite dihydroxyeicosatrienoic acids (DHETs) were measured in the nonclipped kidney. Renal NO synthase (NOS) activity was determined by measuring the rate of formation of L-[(14)C]citruline from L-[(14)C]arginine. RESULTS: Treatment with the sEH inhibitor elicited similar BP decreases that were associated with increases in daily sodium excretion in 2K1C eNOS+/+ as well as 2K1C eNOS-/- mice. In addition, treatment with the sEH inhibitor increased the ratio of EETs/DHETs in the nonclipped kidney of 2K1C eNOS+/+ as well as 2K1C eNOS-/- mice. Treatment with the sEH inhibitor did not alter renal NOS activity in any of the experimental groups. CONCLUSIONS: Collectively, our present data suggest that the BP-lowering effects of chronic sEH inhibition in 2K1C mice are mainly associated with normalization of the reduced availability of biologically active EETs in the nonclipped kidney and their direct natriuretic actions.
- MeSH
- antihypertenziva farmakologie terapeutické užití MeSH
- epoxid hydrolasy antagonisté a inhibitory metabolismus MeSH
- inhibitory enzymů farmakologie terapeutické užití MeSH
- myši inbrední C57BL MeSH
- myši knockoutované MeSH
- myši MeSH
- oxid dusnatý * metabolismus MeSH
- renovaskulární hypertenze farmakoterapie enzymologie MeSH
- synthasa oxidu dusnatého, typ III nedostatek MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- antihypertenziva MeSH
- Ephx2 protein, mouse MeSH Prohlížeč
- epoxid hydrolasy MeSH
- inhibitory enzymů MeSH
- Nos3 protein, mouse MeSH Prohlížeč
- oxid dusnatý * MeSH
- synthasa oxidu dusnatého, typ III MeSH
- MeSH
- angiotensin II krev MeSH
- angiotensin konvertující enzym krev MeSH
- hodnoty glomerulární filtrace účinky léků MeSH
- hydrochlorthiazid terapeutické užití MeSH
- hypertenze farmakoterapie enzymologie MeSH
- inhibitory ACE MeSH
- kaptopril terapeutické užití MeSH
- kombinovaná farmakoterapie MeSH
- krevní tlak * účinky léků MeSH
- krysa rodu Rattus MeSH
- lidé MeSH
- renin-angiotensin systém * účinky léků MeSH
- renin krev MeSH
- renovaskulární hypertenze farmakoterapie enzymologie MeSH
- vodní a elektrolytová rovnováha účinky léků MeSH
- vyšetření funkce ledvin * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- angiotensin II MeSH
- angiotensin konvertující enzym MeSH
- hydrochlorthiazid MeSH
- inhibitory ACE MeSH
- kaptopril MeSH
- renin MeSH
- MeSH
- dospělí MeSH
- lidé MeSH
- renální hypertenze chirurgie MeSH
- renin krev MeSH
- renovaskulární hypertenze diagnóza enzymologie chirurgie MeSH
- venae renales MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- Názvy látek
- renin MeSH
The authors examined 34 patients with arterial hypertension, whose glomerular filtration rate ranged from normal to renal failure. The peripheral plasma renin activity (PRA) values were determined before and 30 and 90 min after injecting furosemide. In 17 patients with chronic renal failure treated by haemodialysis and with arterial hypertension, PRA was likewise determined before and after injecting furosemide. In 18 patients, including 13 from this latter group, PRA was determined before and after dialysis. It was found that: 1) In the group of non-dialysed patients, mean PRA rose significantly after the injection of furosemide. In dialysed patients it was not affected either by furosemide or by dialysis. 2) In non-dialysed patients, the ability of PRA to be stimulated by furosemide fell together with inulin clearance (Cin) in a significant hyperbolic relationship. 3) PRA changes in dialysed patients were indistinct and variable. A significant direct correlation was found between the absolute change in PRA after furosemide and after dialysis. These findings show that the degree of damage to the renal parenchyma must be taken into account when evaluating the response of PRA to furosemide stimulation.
- MeSH
- chronické selhání ledvin enzymologie terapie MeSH
- dialýza ledvin MeSH
- dospělí MeSH
- furosemid farmakologie MeSH
- hypertenze komplikace enzymologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nemoci ledvin komplikace enzymologie MeSH
- renin krev MeSH
- renovaskulární hypertenze enzymologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- furosemid MeSH
- renin MeSH
- MeSH
- dospělí MeSH
- hypertenze enzymologie MeSH
- lecitincholesterolacyltransferasa krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- renální hypertenze enzymologie MeSH
- renovaskulární hypertenze enzymologie MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- Názvy látek
- lecitincholesterolacyltransferasa MeSH
