Endogenous nitric oxide modulates responses of tissue and airway resistance to vagal stimulation in piglets.
The role of endogenous nitric oxide (NO) in modulating the excitatory response of distal airways to vagal stimulation is unknown. In decerebrate, ventilated, open-chest piglets aged 3-10 days, lung resistance (RL) was partitioned into tissue resistance (Rti) and airway resistance (Raw) by using alveolar capsules. Changes in RL, Rti, and Raw were evaluated during vagal stimulation at increasing frequency before and after NO synthase blockade with N(omega)-nitro-L-arginine methyl ester (L-NAME). Vagal stimulation increased RL by elevating both Rti and Raw. NO synthase blockade significantly increased baseline Rti, but not Raw, and significantly augmented the effects of vagal stimulation on both Rti and Raw. Vagal stimulation also resulted in a significant increase in cGMP levels in lung tissue before, but not after, L-NAME infusion. In seven additional piglets after RL was elevated by histamine infusion in the presence of cholinergic blockade with atropine, vagal stimulation failed to elicit any change in RL, Rti, or Raw. Therefore, endogenous NO not only plays a role in modulating baseline Rti, but it opposes the excitatory cholinergic effects on both the tissue and airway components of RL. We speculate that activation of the NO/cGMP pathway during cholinergic stimulation plays an important role in modulating peripheral as well as central contractile elements in the developing lung.
Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106-6010, USA.
Mohammad Y
MY
Khassawneh
Ismail A
IA
Dreshaj
Shijian
S
Liu
Chung-Ho
CH
Chang
Musa A
MA
Haxhiu
Richard J
RJ
Martin
D000403:Airway Resistance / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001993:Bronchodilator Agents / Q000494:pharmacology; D002799:Cholinergic Fibers / Q000502:physiology; D006152:Cyclic GMP / Q000378:metabolism; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006632:Histamine / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D013552:Swine; D014630:Vagus Nerve / Q000502:physiology*
D001993:Bronchodilator Agents; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D001285:Atropine; D006632:Histamine; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester