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

University of Cambridge (2008) Proc Physiol Soc 11, PC119

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

L. M. Bendhack1,2, C. M. Gaitani3, C. N. Lunardi2, M. C. Melo2, F. S. Oliveira2, R. S. Da Silva2

1. Pharmacology, University of Sao Paulo, Ribeirão Preto, Sao Paulo, Brazil. 2. Physics and Chemistry, University of Sao Paulo, Ribeirão Preto, Brazil. 3. Pharmaceutical Sciences, University of Sao Paulo, Ribeirão Preto, Brazil.

View other abstracts by:


Nitrosyl ruthenium complexes have been studied as a new class of NO donors. We have described a new compound (trans-[RuCl([15]aneN4)NO]2+), which in vitro releases NO by the action of a reducing agent such as catecholamines. The NO released from this compound induces vasorelaxation and cytosolic calcium decrease in the vascular smooth muscle cells. The renal hypertension induced by one kidney clipping (2K-1C; performed under tribromoethanol (0.25g/kg i.p.) anaesthesia) presents high sympathetic activity. Therefore, the present study aimed to investigate the effect of this NO donor on the arterial pressure in severe and moderate renal hypertensive 2K-1C rats. We also evaluated the toxicity of the complex in the vascular smooth muscle cells in the concentration used to induce the maximum vasodilatation. The mean arterial pressure (MAP) was measured before and up to six hours after intravenous in bolus injection of trans-[RuCl([15]aneN4)NO]2+ (10 mM/kg) in conscious hypertensive 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 hours after the compound injection. In 2K rats the compound had no hypotensive effect. We have also studied the effect of injection of 0.1 mM/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 there was a significant reduction on the MAP of -28.64 ± 12.45 mmHg, that corresponds to 13.72 ± 5.04% of reduction of the basal MAP. The cell viability after the incubation of vascular smooth muscle cells with 0.1 mM trans-[RuCl([15]aneN4)NO]2+ for 3 h was not toxic as revealed by the MTT assay. The cells viability was 100% in the absence (control) and 97.0 ± 0.5% in the presence of the NO donor. In conclusion, the NO donor reduced the MAP of all hypertensive rats in the dose of 10mM/kg and in the severe hypertensive rats at the dose of 0.1mM/kg. The present investigation showed the hypotensive effect of the new NO donor reinforcing the idea that the use of this compound could be useful in different degrees of hypertension.



Where applicable, experiments conform with Society ethical requirements.

Site search

Filter

Content Type