L-NAME, a nitric oxide synthase inhibitor, as a potential countermeasure to post-suspension hypotension in rats.
A large number of astronauts returning from spaceflight experience orthostatic hypotension. This hypotension may be due to overproduction of vasodilatory mediators, such as nitric oxide (NO) and prostaglandins. To evaluate the role of the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) as a countermeasure against the post-suspension reduction in mean arterial pressure (MAP), we assessed the cardiovascular responses and vascular reactivity to 7-day 30 degrees tail-suspension and a subsequent 6 hr post-suspension period in conscious rats. After a pre-suspension reading, direct MAP and heart rate (HR) were measured daily and every 2 hrs post-suspension. The NO synthase inhibitor L-NAME (20 mg/kg, i.v.), or saline, were administered after the 7th day reading prior to release from suspension and at 2 and 4 hrs post-suspension. At 6 hrs post-suspension, vascular reactivity was assessed. While MAP did not change during the suspension period, it was reduced post-suspension. Heart rate was not significantly altered. L-NAME administration reversed the post-suspension reduction in MAP. In addition, the baroreflex sensitivity for heart rate was modified by L-NAME. Thus, the post-suspension reduction in MAP may be due to overproduction of NO and altered baroreflex activity.
Bayorh
M A
MA
Department of Pharmacology/Toxicology, Morehouse School of Medicine, Atlanta, GA 30310-1495, USA. bayorh@msm.edu
Socci
R R
RR
Watts
S
S
Wang
M
M
Eatman
D
D
Emmett
N
N
Thierry-Palmer
M
M
D000818:Animals; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D019417:Hindlimb Suspension / Q000009:adverse effects / Q000502:physiology; D006801:Humans; D007024:Hypotension, Orthostatic / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013026:Space Flight
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester