PMID- 7934311
OWN - NLM
STAT- MEDLINE
DCOM- 19941107
LR  - 20181130
IS  - 0379-0355 (Print)
IS  - 0379-0355 (Linking)
VI  - 16
IP  - 5
DP  - 1994 Jun
TI  - In vitro vasorelaxant and in vivo cardiovascular effects of S-nitrosothiols: 
      comparison to and cross tolerance with standard nitrovasodilators.
PG  - 323-35
AB  - The in vitro vasorelaxant and in vivo cardiovascular effects of synthetic 
      S-nitrosothiols (RSNOs) were compared to standard nitrovasodilators. 
      S-Nitroso-glutathione (GSNO), S-nitroso-N-acetylcysteine (NACysNO), 
      S-nitroso-galactopyranose (GPSNO), S-nitroso-thioglycerol (TGSNO) and 
      S-nitroso-homocysteine (HCysNO) relaxed phenylephrine (PE) contracted rabbit 
      aorta at 50% effective concentrations (EC50s) of 3-46 nM. While nitroglycerin 
      (GTN) exhibited in vitro tolerance after preincubation, the RSNOs were 
      considerably less cross tolerant to GTN. In conscious dogs, GSNO, NACysNO and 
      GPSNO (1-20 mcg/kg/min i.v.) paralleled nitroprusside (SNP) in reducing mean 
      arterial and central venous pressure (MAP; CVP) with mild tachycardia. GSNO, 
      NACysNO and SNP were more hypotensive and more resistant to isosorbide dinitrate 
      (ISDN) cross tolerance than GTN. NACysNO showed mild self tolerance with low 
      infusion (2.5 mcg/kg/min x 4h x 3 days) and blunted GTN's hypotension. These 
      studies demonstrate that GSNO and NACysNO are SNP-like vasodilators in conscious 
      dogs, which exhibit less cross tolerance to ISDN than GTN. Further, RSNOs relax 
      vascular smooth muscle seemingly independent of nitric oxide (NO) liberation, and 
      nitrate tolerance may involve reduced RSNO formation or NO release rather than 
      desensitized guanylate cyclase (GC).
FAU - Smith, M P
AU  - Smith MP
AD  - Cardiovascular Diseases Unit, Upjohn Laboratories, Upjohn Company, Kalamazoo, MI.
FAU - Humphrey, S J
AU  - Humphrey SJ
FAU - Kerr, S W
AU  - Kerr SW
FAU - Mathews, W R
AU  - Mathews WR
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - Spain
TA  - Methods Find Exp Clin Pharmacol
JT  - Methods and findings in experimental and clinical pharmacology
JID - 7909595
RN  - 0 (Nitroso Compounds)
RN  - 0 (S-Nitrosothiols)
RN  - 0 (Sulfhydryl Compounds)
RN  - 0 (Vasodilator Agents)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 60-24-2 (Mercaptoethanol)
RN  - 67616-44-8 (S-nitrosomercaptoethanol)
SB  - IM
MH  - Animals
MH  - Blood Pressure/drug effects
MH  - Cardiovascular System/*drug effects
MH  - Dogs
MH  - Drug Tolerance
MH  - Female
MH  - Heart Rate/drug effects
MH  - In Vitro Techniques
MH  - Male
MH  - *Mercaptoethanol
MH  - Muscle Relaxation/*drug effects
MH  - Muscle, Smooth, Vascular/*drug effects/metabolism/physiology
MH  - Nitric Oxide/physiology
MH  - Nitroso Compounds/*pharmacology
MH  - Rabbits
MH  - *S-Nitrosothiols
MH  - Sulfhydryl Compounds/*pharmacology
MH  - Time Factors
MH  - Vasodilator Agents/*pharmacology
EDAT- 1994/06/01 00:00
MHDA- 1994/06/01 00:01
CRDT- 1994/06/01 00:00
PHST- 1994/06/01 00:00 [pubmed]
PHST- 1994/06/01 00:01 [medline]
PHST- 1994/06/01 00:00 [entrez]
PST - ppublish
SO  - Methods Find Exp Clin Pharmacol. 1994 Jun;16(5):323-35.