The vasodilator potency of the endothelium-derived relaxing factor, L-S-nitrosocysteine, is impaired in conscious spontaneously hypertensive rats.
OBJECTIVE
This study compared the hemodynamic responses elicited by the endothelium-derived relaxing factor (EDRF), L-S-nitrosocysteine (L-SNC), the non-prostanoid EDRF released by acetylcholine (ACh) and nitric oxide (NO)-donors such as MAHMA NONOate, in conscious spontaneously hypertensive (SH) and normotensive Wistar-Kyoto (WKY) rats.


METHODS
The depressor and/or vasodilator responses elicited by intravenous injections of ACh, L-SNC and MAHMA NONOate were determined in adult WKY and SH rats before and after intravenous injection of the NO synthesis inhibitor, N(G)-nitro-L-arginine methylester (L-NAME), or the cyclooxygenase inhibitor, indomethacin.


RESULTS
The responses elicited by ACh and L-SNC were smaller in SH than in WKY rats whereas the responses elicited by MAHMA NONOate were augmented in SH rats. The ACh-induced responses were not diminished after injection of L-NAME in WKY or SH rats. Indomethacin did not affect the responses to any of the vasodilator agents in WKY or SH rats. Addition of L-SNC to whole blood or thoracic aortae from SH rats yielded similar amounts of NO to those of WKY rats.


CONCLUSIONS
The vasodilator potencies of ACh and L-SNC were diminished whereas that of NO was augmented in SH rats. The loss of potency of L-SNC in SH rats was not obviously due to differences in decomposition to NO or the overactivity of cyclooxygenase factors. This study provides the first evidence that diminished endothelium-dependent vasodilation in SH rats may involve a loss of vasodilator potency of endogenous L-SNC.
Lewis
Stephen J
SJ
Department of Physiology and Pharmacology, Institute of Comparative Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7389, USA. slewis@vet.uga.edu
Hashmi-Hill
Maleka P
MP
Owen
Joy R
JR
Sandock
Kevin
K
Robertson
Tom P
TP
Bates
James N
JN
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure; D003065:Coenzyme A / Q000494:pharmacology; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005263:Femoral Artery / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D006973:Hypertension / Q000201:enzymology / Q000503:physiopathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D026403:S-Nitrosothiols / Q000494:pharmacology*; D013152:Splanchnic Circulation / Q000187:drug effects; D014655:Vascular Resistance; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D026403:S-Nitrosothiols; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; C084625:S-nitroso-coenzyme A; C021315:S-nitrosocysteine; D019001:Nitric Oxide Synthase; D003545:Cysteine; D000109:Acetylcholine; D003065:Coenzyme A; D019331:NG-Nitroarginine Methyl Ester