Hypotensive effect of the nitrosyl ruthenium complex nitric oxide donor in renal hypertensive rats.
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+/-8.70mmHg, n=5), the MAP was reduced in -34.25+/-13.50mmHg (P<0.05) 6h after administration of 10mmol/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 0.1mmol/L/Kg in normotensive (basal 118.20+/-11.25mmHg, n=4), moderate (basal 160.90+/-2.30mmHg, n=6), and severe hypertensive rats (basal 202.46+/-16.74 mmHg, n=6). The compound at the dose of 0.1mmol/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+/-16.70mmHg, n=6) there was a significant reduction on the MAP of -28.64+/-12.45mmHg. The NO donor reduced the MAP of all hypertensive rats in the dose of 10mmol/L/Kg and in the severe hypertensive rats at the dose of 0.1mmol/L/Kg. The compound was not cytotoxic to the rat aortic vascular smooth muscle cells in the concentration of 0.1mmol/L/Kg that produced the maximum relaxation.
de Gaitani
Cristiane Masetto
CM
Departamento de Ciências Farmacêuticas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Avenida do Café s/n, 14040-903 Ribeirão Preto, São Paulo, Brazil. crisgai@fcfrp.usp.br
de Melo
Miriam C C
MC
Lunardi
Claure N
CN
de S Oliveira
Fabiana
F
da Silva
Roberto S
RS
Bendhack
Lusiane M
LM
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001011:Aorta; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000188:drug therapy*; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D020030:Nitric Oxide Donors / Q000627:therapeutic use*; D009942:Organometallic Compounds / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D012428:Ruthenium / Q000627:therapeutic use*; D014664:Vasodilation / Q000187:drug effects
D000959:Antihypertensive Agents; D020030:Nitric Oxide Donors; D009942:Organometallic Compounds; C494411:chloronitrosyl(1,4,8,12-tetraazacyclopentadecane)ruthenium(III); D012428:Ruthenium