NOS II inhibition attenuates post-suspension hypotension in Sprague-Dawley rats.
The reduction in mean arterial pressure observed in astronauts may be related to the impairment of autonomic function and/or excessive production of endothelium-derived relaxing factors. Here, we examined the role of a nitric oxide synthase II (NOS II) inhibitor AMT (2-amino-dihydro-6-methyl-4H-1,3-thiazine) against the post-suspension reduction in mean arterial pressure (MAP) in conscious male Sprague-Dawley rats. Direct MAP and heart rate were determined prior to tail-suspension, daily during the 7-day suspension and every 2 hrs post-suspension. Prior to release from suspension and at 2 and 4 hrs post-suspension, AMT (0.1 mg/kg), or saline, were administered intravenously. During the 7-day suspension, MAP was not altered, nor were there significant changes in heart rate. The reduction in MAP post-suspension in saline-treated rats was associated with significant increases in plasma nitric oxide and prostacyclin. 2-Amino-dihydro-6-methyl4H-1,3-thiazine reduced plasma nitric oxide levels, but not those of prostacyclin, attenuated the observed post-suspension reduction in MAP and modified the baroreflex sensitivity for heart rate. Thus, the post suspension reduction in mean arterial pressure is due, in part, to overproduction of nitric oxide, via the NOS II pathway, and alteration in baroreflex activity.
Eatman
D
D
Departments of Pharmacology/Toxicology, Morehouse School of Medicine, Atlanta, Georgia 30310-1495, USA.
Walton
M
M
Socci
R R
RR
Emmett
N
N
Bayorh
M A
MA
D000818:Animals; D017704:Baroreflex / Q000187:drug effects; D001794:Blood Pressure; D001808:Blood Vessels / Q000187:drug effects; D015232:Dinoprostone / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D011464:Epoprostenol / Q000097:blood; D006339:Heart Rate; D019417:Hindlimb Suspension / Q000009:adverse effects*; D007022:Hypotension / Q000209:etiology* / Q000503:physiopathology*; D008297:Male; D009569:Nitric Oxide / Q000097:blood; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D013843:Thiazines / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000097:blood; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
C093124:2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine; D004791:Enzyme Inhibitors; D013843:Thiazines; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D010656:Phenylephrine; D009569:Nitric Oxide; D013928:Thromboxane A2; D011464:Epoprostenol; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D015232:Dinoprostone