To determine changes in NO-mediated dilatation of pulmonary arteries (PA) and contribution of soluble guanylate cyclase (sGC) -dependent and -independent mechanisms and to evaluate morphological characteristics of PA in rats with unilateral carotid bodies ischemia.
Ligations of left common carotid artery (CCA) or external carotid artery (ECA) were performed on white rats to stop the blood flow in carotid bodies. A month later, inhibition of NO-mediated dilatation of isolated PA was evaluated using sGC blocker (ODQ) and K+-channels antagonists (glibenclamide for K+ATP channels and tetraethylammonium (TEA) for K+v-channels). Sodium nitroprusside (SNP) was used as a donor of NO. Phosphodiesterase V blocker (Zaprinast) was used for evaluation of sGC-dependent vasodilation. Morphological characteristics of small PA, relative mass of right ventricle (RV) and systolic pressure (SBP) in RV were evaluated.
ODQ blocked dilatation in rats with unilateral ischemia of the carotid body more effectively than in control group (p < 0,05). There was no difference in PA relaxation in response to Zaprinast between the experimental and the control groups. TEA reduced PA relaxation with SNP at concentrations from 10-9 to 10-7 M in the control group and at concentrations from 10-10 to 10-8 M in the experimental group (p < 0,05). Glibenclamide significantly inhibited relaxation in the control group but it had no effect on NO-mediated dilatation in the experimental group. There were structural changes in PA of the rats with unilateral ligation of CCA or ECA: area of the media increased by 20% and 50% respectively (p < 0,05). The number of layers of smooth muscle and relative mass of RV did not change, but SBP in RV increased by 19,5% (p < 0,05).
We suspect a mechanism associated with carotid bodies which can be a sufficient stimulus for pulmonary hypertension development. Moderate hypertrophy of PA was found in experimental groups, so this did not reflect on the mass of RV but increased SBP in RV. Hypertrophy of PA increased the contribution of sGC. This may be the result of the decreased contribution of independent from sGC mechanism which is the direct activation of K+-channels by NO.
Lomonosov Moscow State University, Faculty of Medicine, Department of Physiology and Pathology, Moscow, Russia