ИСТИНА

Background: Pulmonary hypertension (PH) is a condition characterized by constitutively increased pressure in pulmonary arteries (PA) and can be caused by different factors, including an increase of sympathetic nervous system (SNS) tone. Carotid bodies (CB) activation by hypoxia or carotid arteries (CA) ischemia increases SNS tone. Transitory increase of PA pressure was found during local action of NaCN on CB of one of the CA in rats. However, the effect of longterm unilateral ischemia of CB is not studied yet, and we propose that it may be an independent mechanism of PH. Purpose: To evaluate morphological features of PA and to determine changes in structure of NOmediated dilatation of PA and hemodynamic parameters in rats with unilateral ischemia of CB. Methods: Ligation of left common CA was performed on white rats to stop the blood flow in CB. A month later, inhibition of NOmediated dilatation of isolated PA of the second order was evaluated using sGC blocker ODQ and Kchannels antagonists (glibenclamide for KATP channels and tetraethylammonium for Kvchannels). Sodium nitroprusside (SNP, 10–11–10–7 M) was used as a donor of NO. Relative mass of right ventricle (RV) and systolic pressure (SBP) in RV were also evaluated. Hemodynamic parameters (systemic blood pressure, heart rate, cardiac baroreflex sensitivity) were measured in conscious rats, where CB ischemia was obtained by ligation of external CA, because in this group CB ischemia did not accompany any disorders of blood supply of the brain. Area of media of PA (diameter <300μm) normalised to vessel diameter were measured in both parts of the experiments. Results: The baroreflex sensitivity, measured by SNP, decreased in rats with CB ischemia (1,53 Δmm Hg/ ΔBPM vs 2,62 Δmm Hg/ΔBPM, p<0,05), whereas the response to α1agonist phenylephrine, did not change. This reflects the alteration of SNS activity in experimental group. Functional and structural changes of PA were also obtained. The response to SNP when using ODQ decreased in rats with CB ischemia. Inhibition of relaxation was found in all the concentrations used in the experiment (p<0,05), whereas ODQ blocked dilatation of the vessels in control group only with SNP at high concentrations (≥10–8 M). Glibenclamide significantly inhibited the relaxation in the control group but it had virtually no effect on NOmediated dilatation in the experimental group. Normalised area of the media increased in both experimental groups (p<0,05). There was no hypertrophy of RV in experimental groups, but SBP in RV increased (36 mm Hg vs 30 mm Hg, p<0,05).