Does central nitric oxide elicit pulmonary hypertension in conscious rats?
The mechanisms involved in the pathogenesis of pulmonary arterial hypertension (PAH) remain unclear. Nitric oxide (NO) centrally attenuates sympathetic outflow and, therefore, may chronically modulate pulmonary arterial pressure (PAP), especially during the development of chronic hypoxia-induced PAH. To test this hypothesis, 20 male Sprague-Dawley rats (B.W. approximately 200-320 g) were chronically implanted with a telemetric transmitter for the continuous measurement of PAP, and an osmotic pump for intracerebroventricular (i.c.v.) administration of either aCSF (control), L-NAME (150 microg/kg/day) or the NO-donor, SIN-1 (100 microg/kg/day). Rats spent 7 days in normoxia, and then 14 days in hypoxia (CH=12% O2). In normoxia, exogenous NO elevated PAP by approximately 64%, although this increase in PAP could be prevented by isoproterenol (200 mug/kg). PAH occurred in all rats following 14 days of hypoxia. L-NAME did not alter baseline MPAP or the physiological responses to hypoxia. Our results suggest that central NO increases MPAP, although the mechanisms involved remain to be fully elucidated.
Schwenke
Daryl O
DO
Department of Cardiac Physiology, National Cardiovascular Center Research Institute, Suita, Osaka, Japan. schwenke@ri.ncvc.go.jp
Pearson
James T
JT
Mori
Hidezo
H
Shirai
Mikiyasu
M
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000201:enzymology* / Q000209:etiology*; D000860:Hypoxia / Q000150:complications; D015918:Infusion Pumps, Implantable; D007276:Injections, Intraventricular / Q000379:methods; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008981:Molsidomine / Q000008:administration & dosage / Q000031:analogs & derivatives; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000008:administration & dosage; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013686:Telemetry / Q000379:methods; D013997:Time Factors; D014851:Wakefulness
D000318:Adrenergic beta-Agonists; D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; C002385:linsidomine; D008981:Molsidomine; D007545:Isoproterenol; D019331:NG-Nitroarginine Methyl Ester