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J Appl Physiol (April 19, 2002). doi:10.1152/japplphysiol.01078.2001
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Articles in PresS, published online ahead of print April 19, 2002
J Appl Physiol, 10.1152/jap.01078.2001
Submitted on October 29, 2001
Accepted on January 21, 2002

Endogenous Nitric Oxide Modulates Responses of Tissue and Airway Resistance to Vagal Stimulation in Piglets

Mohammad Y Khassawneh1, Ismail A Dreshaj1, Shijian Liu1, Chung-Ho Chang1, Musa A Haxhiu2, and Richard J Martin1*

1 Department of Pediatrics, Case West Reserve University School of Medicine, Cleveland, OH, USA
2 Department of Pediatrics, Case West Reserve University School of Medicine, Cleveland, OH, USA; Department of Physiology/Biophysics, Howard University College Medicine, Washington, DC, USA

* To whom correspondence should be addressed. E-mail: rxm6{at}po.cwru.edu.

The role of endogenous nitric oxide in modulating the excitatory response of distal airways to vagal stimulation is unknown. In decerebrate, ventilated, open-chested piglets aged 3-10 days, lung resistance [RL] was partitioned into tissue resistance [Rti] and airway resistance [Raw] using alveolar capsules. Changes in RL, Rti, and Raw were evaluated during vagal stimulation at increasing frequency before and after nitric oxide synthase [NOS] blockade with N{omega}-Nitro-L-Arginine Methyl Ester [L-NAME]. Vagal stimulation increased RL by elevating both Rti and Raw. NOS 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 prior to, 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.




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