Submitted on July 15, 2005
Accepted on March 17, 2006
Adjacent Bronchus Attenuates Pulmonary Arterial Contractility
Satyan Lakshminrusimha1*, James A Russell2, Sylvia F Gugino3, Rita M Ryan1, Bobby Mathew4, Lori C Nielsen4, and Frederick C Morin III1
1 Pediatrics, State University of New York, Buffalo, New York, United States
2 Pediatrics, State University of New York, Buffalo, New York, United States; Physiology and Biophysics, State University of New York , Buffalo, New York, United States
3 Physiology and Biophysics, State University of New York, Buffalo, New York, United States
4 Pediatrics, State University of New York, Buffalo, New York, United States; Physiology and Biophysics , State University of New York, Buffalo, New York, United States
* To whom correspondence should be addressed. E-mail: slakshmi{at}buffalo.edu.
Bronchial derived relaxing factor (BrDRF) decreases the contractility of newborn rat pulmonary arteries (PA) and is dependent on nitric oxide (NO) synthesis. In vivo, this factor appears to gain access via the adventitial side of the PA. However, the adventitia has been reported to be a barrier to NO. We studied the effect of an adjacent bronchus on PA contractility to norepinephrine in nine juvenile lambs in the presence and absence of inhibitors of the NO pathway (LNA, ODQ and Rp-8-Br-PET-cGMPS), cytochrome p450 inhibitor (17 ODY-A), perivascular nerve activity blocker (TTX), superoxide scavenger (tiron) and following disruption of bronchial epithelium. We also evaluated whether BrDRF was effective on both the endothelial and/or adventitial side of PA. Fifth generation PA rings with and without an attached bronchus were contracted in standard baths with norepineprhine. PA were dissected, cut open and placed in a sided chamber in which the adventitial and endothelial sides of the PA were exposed to unattached bronchus separately. Norepinephrine (10-8-10-5M) contractions were expressed as a fraction of maximal KCl (118mM) contractions. Norepinephrine contractions were significantly reduced by the presence of an attached bronchus, an effect that was reversed by pretreatment with LNA, ODQ, Rp-8-Br-PET-cGMPS and removal of bronchial epithelium. Unattached bronchus in the bath perfusing the adventitial side was effective in inhibiting the contractile response in PA. NO gas relaxed PA when administered on the endothelial side only. We speculate that BrDRF is a diffusible factor that crosses the adventitia and stimulates production of NO within the PA.
