Vitamin C improves the effect of a new nitric oxide donor on the vascular smooth muscle from renal hypertensive rats.
Impaired relaxation induced by the new nitric oxide (NO) donor [Ru(NH.NHq)(terpy)NO(+)](3+) (TERPY) has been observed in the aortic rings from renal hypertensive rats (2K-1C). An increased production of reactive oxygen species (ROS) in the aortas from 2K-1C rats are capable of reducing NO bioavailability. Therefore, this study aimed at investigating the effects of an antioxidant (vitamin C) on the relaxant effect of NO released from TERPY on the 2K-1C rat aorta. As for vascular reactivity, the potency of TERPY is greater in the control rats (2K) than in 2K-1C whereas the maximum relaxation (ME) is not significantly different between the 2K and 2K-1C rat aortas. The relaxation of TERPY is potentiated only in the 2K-1C aortic ring treated with vitamin C. TERPY has a lower effect in decreasing cytosolic Ca(2+) concentration ([Ca(2+)]c) in vascular smooth muscle cells (VSMCs) from 2K-1C rats. This effect is also potentiated in 2K-1C aortic cells treated with vitamin C, but it is not altered in 2K cells. The basal cytosolic NO concentration ([NO]c) is lower in 2K-1C than in 2K cells, and the bioavailability of the NO released from TERPY is larger in 2K than in 2K-1C VSMCs. The superoxide radical concentration ([O(2)(*-)]) is higher in the 2K-1C aorta, and vitamin C reduces the [O(2)(*-)] in the 2K-1C aorta. Taken together, these results show that in the aortas of renal hypertensive 2K-1C rats, released NO from the new NO donor is not available to produce a similar effect in 2K aorta due to increased [O(2)(*-)].
Rodrigues
G J
GJ
Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, USP, 14040-903 Ribeirão Preto, SP, Brazil.
Lunardi
C N
CN
Lima
R G
RG
Santos
C X
CX
Laurindo
F R M
FR
da Silva
R S
RS
Bendhack
L M
LM
D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000473:pathology; D001205:Ascorbic Acid / Q000494:pharmacology*; D002118:Calcium / Q000032:analysis / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006977:Hypertension, Renal / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D009569:Nitric Oxide / Q000032:analysis / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009924:Organ Culture Techniques; D009942:Organometallic Compounds / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012428:Ruthenium / Q000737:chemistry; D013481:Superoxides / Q000032:analysis / Q000378:metabolism; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects
D020030:Nitric Oxide Donors; D009942:Organometallic Compounds; D013481:Superoxides; D010656:Phenylephrine; D009569:Nitric Oxide; D012428:Ruthenium; D001205:Ascorbic Acid; D002118:Calcium