DOI, a 5-HT2 receptor agonist, induces renal vasodilation via nitric oxide in anesthetized dogs
| Autor: | Ming-Sheng Zhou, Run-Xian Tian, Matlubur Rahman, Naoki Kondou, Yoshihide Fujisawa, Hirohito Yoneyama, Akira Nishiyama, Shoji Kimura, Hiroaki Kosaka, Youichi Abe |
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| Rok vydání: | 2002 |
| Předmět: |
Male
medicine.medical_specialty Renal cortex Sarpogrelate Vasodilation Kidney Nitric Oxide Nitric oxide chemistry.chemical_compound Dogs Internal medicine medicine Animals Anesthesia Enzyme Inhibitors Cyclic GMP Nitrites Pharmacology Nitrates Hemodynamics Kidney metabolism Succinates humanities Serotonin Receptor Agonists Endocrinology medicine.anatomical_structure Indophenol NG-Nitroarginine Methyl Ester chemistry Renal physiology Renal blood flow Receptors Serotonin Female Serotonin Antagonists Nitric Oxide Synthase |
| Zdroj: | European journal of pharmacology. 437(1-2) |
| ISSN: | 0014-2999 |
| Popis: | We have previously reported that (+/-)-1-(2.5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a 5-HT2 receptor agonist, induced renal vasodilation in anesthetized dogs. The present study was designed to investigate whether DOI-induced renal vasodilation might be mediated by increased nitric oxide (NO) release/production in renal tissue. The experiments were performed in anesthetized dogs. A 23-gauge needle was inserted into the left renal artery for infusion of drug solutions. Renal blood flow was measured with an electromagnetic flowmeter. The microdialysis probes were implanted into the renal cortex to collect the dialysate for measurement of guanosine 3',5'-cyclic monophosphate (cGMP) and nitrite/nitrate (NO2/NO3) concentration. Intrarenal infusion of DOI at a rate of 5 microg/kg/min resulted in a significant increase, by 30 +/- 4%, in renal blood flow, indicating renal vasodilation. The renal interstitial concentrations of NO2/NO3 and cGMP also increased by 70 +/- 6% and 60 +/- 6%, respectively. These changes induced by DOI were completely abolished by the intrarenal pretreatment with N(w)-nitro-L-arginine methyl ester (L-NAME, a NO synthase inhibitor, 100 microg/kg/min) or sarpogrelate (100 microg/kg/min, a highly selective 5-HT2 receptor antagonist). DOI infusion increased urine volume and urinary excretion of Na+, which were also blocked by L-NAME or sarpogrelate. These results suggest that DOI caused renal vasodilation due to increased NO release/production by stimulation of 5-HT2 receptors in the kidney. The natriuretic effect of DOI might also be related to increased intrarenal NO production. |
| Databáze: | OpenAIRE |
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