Endothelial nitric oxide has inhibitory effects on rhythmic contractions in the aortas of sinoaortic deafferented rats.
Sinoaortic deafferentation (SAD) is characterized by arterial pressure lability, without sustained hypertension. Although SAD rats did not become hypertensive, their isolated aortas exhibit RCs. We have investigated whether these RCs are influenced by endothelium. Aortic rings were placed in an organ chamber, and the frequency and amplitude of the RCs were measured in SAD rat aortas with intact and denuded endothelium. Moreover, the participation of endothelial NO and cGMP pathways on the RCs were analyzed through the use of such drugs as L-NAME, acetylcholine, ODQ, L-arginine, and oxyhemoglobin. Indomethacin was used to evaluate the influence of prostanoids on the RCs. Under phenylephrine stimulus, 100% of SAD rat aortas presented RCs, with higher frequency and amplitude in denuded endothelium (8.5 +/- 0.50 cycles/2 min and 0.465 +/- 0.05 g, respectively) compared with intact endothelium (4.5 +/- 0.50 cycles/2 min and 0.311 +/- 0.04 g, respectively). In intact-endothelium aortas, L-NAME, ODQ, and oxyhemoglobin raised the frequency and amplitude of the RCs to values similar to those found in denuded endothelium. L-arginine and indomethacin did not alter the RCs. In conclusion, SAD rat aortas present rhythmic contractions, which are negatively modulated by endothelial NO. Our results indicate that endothelium-derived NO (and not prostanoids), acting through the cGMP pathway, has an inhibitory effect on the oscillations.
Rocha
Matheus L
ML
Department of Pharmacology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.
Bendhack
Lusiane M
LM
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D001120:Arginine / Q000494:pharmacology; D017763:Autonomic Denervation; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D006339:Heart Rate / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D010108:Oxyhemoglobins / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D004791:Enzyme Inhibitors; D010069:Oxadiazoles; D010108:Oxyhemoglobins; D011810:Quinoxalines; D009599:Nitroprusside; D010656:Phenylephrine; D009569:Nitric Oxide; D001120:Arginine; D006162:Guanylate Cyclase; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin