Response of normoxic pulmonary arteries of the rat in the resting and contracted state to NO synthase blockade.
1. The pulmonary vasculature is normally in a low resting state of tone. It has been hypothesized that this basal tone is actively maintained by the continuous release of a vasodilator in the resting state. However, evidence for basal release of nitric oxide (NO) is inconclusive. 2. We studied the release of NO in arteries from the pulmonary circulation of male Wistar-Kyoto rats by examining the effects of the L-arginine analogue NG-nitro-L-arginine methyl ester (L-NAME) on resting pulmonary arteries and on vessels pre-contracted with prostaglandin F2(alpha) (PGF2 alpha). 3. Rats (n = 21) were killed by an overdose with pentobarbitone. Pulmonary arteries were dissected (mean internal diameter 459 +/- 11 microns) and mounted in a small vessel wire myograph. Resting tensions were to set to stimulate transmural pressures of 17.5 mmHg. 4. L-NAME (100 microM) was found to produce a contraction of 0.64 +/- 0.09 mN mm-1 in resting pulmonary arteries when added alone to the myograph bath. This contraction was not produced following removal of the endothelium. Vessel contraction to PGF(2 alpha) (100 microM) was found to be significantly greater when carried out in the presence of L-NAME (100 microM) -1.37 +/- 0.15 mN mm-1 compared with 1.96 +/- 0.17 mN mm-1. Dilation following acetylcholine (ACh) (1 microM) was abolished in the presence of L-NAME (100 microM). 5. Rat pulmonary artery contraction in response to the addition of L-NAME and the absence of contraction upon removal of the endothelium provides supportive evidence of the active release of nitric oxide for the maintenance of resting tone.
Steeds
R P
RP
Department of Cardiology, Royal Hallamshire Hospital, Sheffield.
Thompson
J S
JS
Channer
K S
KS
Morice
A H
AH
D000818:Animals; D001835:Body Weight / Q000502:physiology; D015237:Dinoprost / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D011651:Pulmonary Artery / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D011921:Rats, Inbred WKY; D014661:Vasoconstriction / Q000187:drug effects
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D015237:Dinoprost; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester