title: Role of endothelium-derived relaxing factors in the renal response to vasoactive agents in hypothyroid rats.
abstract: This study analyzed the role of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) in the abnormal renal vascular reactivity of hypothyroid rats. Renal responses to vasoconstrictors [VC: phenylephrine (PHE) and ANG II] and vasodilators [VD: ACh, sodium nitroprusside (SNP), and papaverine (PV)] were studied in kidneys from control and hypothyroid rats under normal conditions and after NO or EDHF blockade. NO was blocked by the administration of Nomega-nitro-l-arginine methyl ester (l-NAME) and EDHF by the administration of tetraethylammonium (TEA) or by an increased extracellular K+. The response to VC was also evaluated after endothelium removal. Hypothyroid kidneys showed reduced responsiveness to PHE and a normal response to ANG II. l-NAME and TEA administration produced an increased sensitivity to PHE and to ANG II in control preparations. l-NAME also increased the response to PHE in hypothyroid kidneys, but the differences between control and hypothyroid kidneys were maintained. TEA administration did not change the response to either VC in hypothyroid preparations. In endothelium-removed preparations, TEA was unable to increase pressor responsiveness to VC. Hypothyroid kidneys showed reduced responsiveness to ACh and SNP and normal response to PV. The differences between hypothyroid and control preparations in the responses to ACh and SNP were maintained after l-NAME or increased K+. In conclusion, this study shows that 1) the attenuated response to PHE in hypothyroidism is not related to an increased production of endothelium-derived relaxing factors NO and EDHF; 2) the response to VC in hypothyroid preparations is insensitive to EDHF blockade; and 3) hypothyroid preparations have a reduced reactivity to the NO donor, and NO-independent vasodilatation remains unaffected.
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Hospital Virgen de las Nieves, Granada, Spain.
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Moreno
authors.forename: Rosemary
authors.initials: R
authors.lastname: Wangensteen
authors.forename: Juan
authors.initials: J
authors.lastname: Sainz
authors.forename: Isabel
authors.initials: I
authors.lastname: Rodríguez-Gomez
authors.forename: Virginia
authors.initials: V
authors.lastname: Chamorro
authors.forename: Antonio
authors.initials: A
authors.lastname: Osuna
authors.forename: Félix
authors.initials: F
authors.lastname: Vargas
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001685:Biological Factors / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007037:Hypothyroidism / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052250:Nitric Oxide Synthase Type III; D010656:Phenylephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D001685:Biological Factors; D004791:Enzyme Inhibitors; D013757:Tetraethylammonium Compounds; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; D014284:Triiodothyronine; D000804:Angiotensin II; D010656:Phenylephrine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D013974:Thyroxine; D011188:Potassium; D019331:NG-Nitroarginine Methyl Ester