Modulation of baroreceptor activity by nitric oxide and S-nitrosocysteine.
The goal of this study was to determine whether nitric oxide (NO) and the NO donor, S-nitrosocysteine (cysNO), modulate the activity of carotid sinus baroreceptors. Baroreceptor activity was recorded from the vascularly isolated carotid sinus in anesthetized rabbits. Baroreceptor activity decreased in a dose-dependent manner after injection of either NO or cysNO as constant pressure was maintained, and activity recovered spontaneously over time, within seconds to minutes. The baroreceptor pressure-activity relation was shifted significantly to the right by cysNO, with a profound suppression of activity at high pressure. Baroreceptor activity at 160 mm Hg averaged 76 +/- 8%, 60 +/- 6%, and 36 +/- 5% of the control maximum during exposure to 10(-4), 2 to 3 x 10(-4), and 10(-3) mol/L cysNO, respectively. The inhibition of activity by the L and D isomers of cysNO was equivalent and was blocked by reduced hemoglobin, suggesting that the effect was mediated by NO. The suppression of baroreceptor activity by cysNO was not related to vascular relaxation as measured by videomicrometer. Inhibition of soluble guanylate cyclase with methylene blue or 6-anilinoquinoline-5,8-quinone (LY83583, 10(-5) mol/L) did not attenuate and dibutyryl cGMP (10(-3) mol/L) did not mimic the suppression of baroreceptor activity by cysNO, suggesting a cGMP-independent mechanism. Activation of endogenous NO formation with thimerosal (10(-5) to 10(-4) mol/L) reduced maximum baroreceptor activity in five of eight experiments to 59 +/- 7% of the control maximum.(ABSTRACT TRUNCATED AT 250 WORDS)
Cardiovascular Center, University of Iowa, Iowa City.
T
T
Matsuda
J N
JN
Bates
S J
SJ
Lewis
F M
FM
Abboud
M W
MW
Chapleau
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002346:Carotid Sinus / Q000187:drug effects* / Q000502:physiology; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D006162:Guanylate Cyclase / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000494:pharmacology*; D011311:Pressoreceptors / Q000187:drug effects* / Q000502:physiology; D011817:Rabbits; D026403:S-Nitrosothiols
D026403:S-Nitrosothiols; D009569:Nitric Oxide; C021315:S-nitrosocysteine; D001120:Arginine; D006162:Guanylate Cyclase; D003545:Cysteine; D019331:NG-Nitroarginine Methyl Ester