Nitric oxide and nitroglycerin reversal of pulmonary vasoconstriction induced by alpha-activation during exercise.
We have previously shown in sheep that pulmonary vascular resistance decreases rapidly after the onset of constant exercise, followed by a slower and smaller second vasodilation. The second phase is partly regulated by alpha- and beta-adrenoceptor activation. We examined the effect of inhaled nitric oxide (NO; 40 ppm) and intravenous nitroglycerin on beta-adrenergic blockade-induced pulmonary vasoconstriction during exercise. In paired studies, we exercised eight sheep at a constant rate of 4 miles per hour for 4 min on a treadmill and measured the hemodynamic response during beta-blockade (propranolol, 1 mg i.v.) with and without 40 ppm inhaled NO or continuous infusion of nitroglycerin (3.2-4.0 micrograms.kg-1.min-1). beta-Blockade resulted in a higher pulmonary vascular resistance during steady-state exercise (40-240 s) than in the unblocked state; reduction in pulmonary vascular resistance during the second phase of exercise was smaller with beta-blockade (13-16%) than with control exercise (26-30%). Inhaled NO and nitroglycerin reversed the beta-blockade-related pulmonary vasoconstriction to the levels of control exercise. Inhaled NO and intravenous nitroglycerin also reversed the pulmonary vasoconstriction produced by intravenous phenylephrine at rest. We conclude that exogenous NO, delivered by gas inhalation or via nitroso compounds, opposes and fully reverses alpha-receptor-activated pulmonary vasoconstriction during exercise in sheep.
Koizumi
T
T
Center for Lung Research, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Hermo
C I
CI
Bjertnaes
L J
LJ
Banerjee
M
M
Newman
J H
JH
Kubo
K
K
D000280:Administration, Inhalation; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage; D000818:Animals; D007262:Infusions, Intravenous; D009569:Nitric Oxide / Q000008:administration & dosage*; D005996:Nitroglycerin / Q000008:administration & dosage*; D010805:Physical Conditioning, Animal / Q000502:physiology; D011652:Pulmonary Circulation / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D012756:Sheep; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000008:administration & dosage*
D000319:Adrenergic beta-Antagonists; D011942:Receptors, Adrenergic, alpha; D014665:Vasodilator Agents; D009569:Nitric Oxide; D005996:Nitroglycerin