Blockers of the L-arginine-nitric oxide-cyclic GMP pathway facilitate baroreceptor resetting.
We investigated the role of nitric oxide on rapid (25- and 40-minute) baroreceptor resetting during the onset of acute hypertension in rats treated with NG-nitro-L-arginine, an inhibitor of nitric oxide synthesis, and methylene blue, an inhibitor of guanylate cyclase. The effect of treatment with glibenclamide, an ATP-dependent K+ channel blocker, was also investigated. Arterial hypertension was provoked in a ramp progression by the drug NG-nitro-L-arginine alone or in association with aortic coarctation. Whole aortic nerve activity and carotid pressure were recorded in the anesthetized rats. The extent of rapid resetting was evaluated by means of the ratio (delta Systolic Threshold Pressure/delta Control Diastolic Pressure) x 100 as well as by the extent of displacement of the pressure-nerve activity curve defined by the ratio (delta Mean Arterial Pressure at 50% of maximum activity/delta Mean Arterial Pressure) x 100. All groups gave the same increase in mean arterial pressure at 25 and 40 minutes after the onset of hypertension. A greater extent of resetting to hypertensive levels was observed in the treated groups compared with coarctation alone. At 40 minutes after the onset of hypertension, the coarctation and nitro-L-arginine groups exhibited a further increase in the extent of resetting. The rats submitted to glibenclamide plus coarctation presented a slight but significant decrease in gain. These findings suggest that an active L-arginine-nitric oxide-cyclic GMP pathway blunts rapid resetting during the onset of hypertension. In addition, they also indicate that ATP-dependent K+ channels can also modulate rapid resetting of the baroreceptors to hypertensive levels.
da Silva
S V
SV
Department of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo, Brazil.
da Silva
V J
VJ
Ballejo
G
G
Salgado
M C
MC
Salgado
H C
HC
D000704:Analysis of Variance; D000818:Animals; D001011:Aorta / Q000294:innervation*; D001017:Aortic Coarctation; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D006152:Cyclic GMP / Q000037:antagonists & inhibitors / Q000502:physiology*; D005905:Glyburide / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000294:innervation*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D019335:Nitroarginine; D011311:Pressoreceptors / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D005905:Glyburide; D008751:Methylene Blue