Hypotensive effect of the nitrosyl ruthenium complex nitric oxide donor in renal hypertensive rats

• Published in: Nitric oxide 2009-05, Vol.20 (3), p.195-199
• Main Authors: de Gaitani, Cristiane Masetto, de Melo, Miriam C.C., Lunardi, Claure N., de S. Oliveira, Fabiana, da Silva, Roberto S., Bendhack, Lusiane M.
• Format: Article
• Language: English
• Subjects: Animals; Antihypertensive Agents - pharmacology; Aorta; Arterial pressure; Dose-Response Relationship, Drug; Hypertension - drug therapy; Muscle, Smooth, Vascular - cytology; Nitric oxide; Nitric Oxide Donors - therapeutic use; NO donor; Organometallic Compounds - therapeutic use; Rats; Rats, Inbred Strains; Renal hypertension; Ruthenium - therapeutic use; Vasodilation - drug effects
• ISSN: 1089-8603; 1089-8611
• DOI: 10.1016/j.niox.2008.12.002

We have described a new compound ( trans-[RuCl([15]aneN 4)NO] 2+), which in vitro releases NO by the action of a reducing agent such as catecholamines. We investigated the effect of this NO donor in lowering the mean arterial pressure (MAP) in severe and moderate renal hypertensive 2K-1C rats. MAP was measured before and after intravenous in bolus injection of the compound in conscious 2K-1C and normotensive (2K) rats. In the hypertensive rats (basal 196.70 ± 8.70 mmHg, n = 5), the MAP was reduced in −34.25 ± 13.50 mmHg (P < 0.05) 6 h after administration of 10 mmol/L/Kg of the compound in bolus. In normotensive rats the compound had no effect. We have also studied the effect of the injection of 0.1 mmol/L/Kg in normotensive (basal 118.20 ± 11.25 mmHg, n = 4), moderate (basal 160.90 ± 2.30 mmHg, n = 6), and severe hypertensive rats (basal 202.46 ± 16.74 mmHg, n = 6). The compound at the dose of 0.1 mmol/L/Kg did not have effect ( P > 0.05) on MAP of normotensive and moderate hypertensive rats. However, in the severe hypertensive rats (basal 202.46 ± 16.70 mmHg, n = 6) there was a significant reduction on the MAP of −28.64 ± 12.45 mmHg. The NO donor reduced the MAP of all hypertensive rats in the dose of 10 mmol/L/Kg and in the severe hypertensive rats at the dose of 0.1 mmol/L/Kg. The compound was not cytotoxic to the rat aortic vascular smooth muscle cells in the concentration of 0.1 mmol/L/Kg that produced the maximum relaxation.