title: Effects of tempol and candesartan on neural control of the kidney.
abstract: We compared the effects of tempol (300 μmol kg(-1) plus 300 μmol kg(-1) h(-1), n=14) and candesartan (10 μg kg(-1) plus 10 μg kg(-1) h(-1), n=14) on renal haemodynamics, excretory function, and responses to electrical stimulation of the renal nerves (RNS) in lean and obese rabbits under pentobarbitone anaesthesia. Depressor responses to tempol (-16 ± 2 mmHg) and candesartan (-12 ± 1 mmHg) were similar. Candesartan, but not tempol, significantly increased basal renal blood flow (RBF; +36 ± 7%). Tempol, but not candesartan, significantly reduced glomerular filtration rate (GFR; -30 ± 10%) and sodium excretion (U(Na)V; -44 ± 14%). RNS induced frequency-dependent reductions in RBF (-20 ± 3% at 1 Hz), GFR (-28 ± 6% at 1 Hz) and U(Na)V (-55 ± 6% at 1 Hz). Candesartan blunted these responses. Tempol did not significantly alter RBF and GFR responses to RNS but blunted the U(Na)V response. Responses to RNS, and the effects of tempol and candesartan, were similar in lean compared with obese rabbits. Unlike candesartan, tempol did not induce renal vasodilatation, maintain GFR and U(Na)V during reductions in arterial pressure, or blunt neurally-mediated vasoconstriction. In conclusion, unlike the AT(1)-receptor antagonist candesartan, tempol does not blunt the effects of RNS on renal haemodynamic function. Furthermore, under the current experimental conditions superoxide appears to make little contribution to the actions of endogenous angiotensin II on baseline renal haemodynamics or excretory function, or their responses to RNS.
authors.affiliation: Department of Physiology, Monash University, Melbourne, Australia.
authors.forename: Gabriela A
authors.initials: GA
authors.lastname: Eppel
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Head
authors.forename: Kate M
authors.initials: KM
authors.lastname: Denton
authors.forename: Roger G
authors.initials: RG
authors.lastname: Evans
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D004032:Diet; D059305:Diet, High-Fat; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006339:Heart Rate / Q000187:drug effects; D006400:Hematocrit; D007668:Kidney / Q000187:drug effects* / Q000294:innervation*; D007677:Kidney Function Tests; D008297:Male; D009765:Obesity / Q000503:physiopathology; D011817:Rabbits; D012079:Renal Circulation / Q000187:drug effects; D013113:Spin Labels; D013481:Superoxides / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology*; D014563:Urodynamics / Q000187:drug effects
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000975:Antioxidants; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D003497:Cyclic N-Oxides; D013113:Spin Labels; D013777:Tetrazoles; D013481:Superoxides; D000804:Angiotensin II; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; C081643:candesartan; C001803:tempol