Effects of LNAME infusion on the pulmonary vascular tone of WT mice at thoracotomy We studied the hemodynamic effects of acute inhibition of NOS by LNAME around the pulmonary vasculature (n=7). Infusion of LNAME (100 mg g1) decreased HR (5801 vs. 5471 beats in1, P=0.049) and markedly increased SAP at 3 minutes (92 vs. 133 mmHg, P=0.0001). Pulmonary arterial pressure did not modify and QLPA decreased slightly right after therapy with LNAME, even so LPVRI was unchanged when compared to untreated animals (67 vs. 67 mmHg in l1). Hemodynamic effects of U46619 infusion around the pulmonary vascular tone of WT mice at thoracotomy To confirm the potential of the pulmonary vasculature to vasoconstrict in anesthetized mice a potent vasoconstrictor, the thromboxane agonist U46619, was infused i.v. at 1.5 mol g1 in1 for 2 minutes. Administration of U46619 to WT mice (n=6) markedly enhanced SAP, PAP, and LPVRI and decreased QLPA (Table 1, Figures two and 3). In more experiments (n=5), we measured QLTAF and LAP before and just after infusion of U46619 and calculated an estimate of TSVR and pulmonary vascular resistance (PVR). Administration of U46619 markedly improved TSVR (2494 vs. 899 mmHg in l1, P=0.001) and PVR (36 vs. 1030 mmHg in l1, P=0.01) and decreased QLTAF devoid of altering LAP (Figure 3). Administration of cellfree Hb to diabetic (db/db) mice at thoracotomy To explore no matter whether endothelial dysfunction developed by diabetes, which sensitizes the systemic circulation for the NO scavenging effects of Hb [21], would alter the pulmonary vascular response to i.v. infusion of Hb in mice, we measured LPVRI before and 3 minutes immediately after infusion of Hb in db/db mice breathing at FIO2 1.0. Infusion of Hb markedly enhanced SAP from 93 to 154 mmHg (P=0.001) in db/db mice (n=5) at three minutes, but did not modify PAP, HR, and QLPA (data not shown) or LPVRI (Figure four). Administration of cellfree Hb, LNAME or saline resolution to WT mice 30 minutes prior to generating unilateral left lung hypoxia by LMBO To ascertain the influence of infusing Hb on HPV in mice, we examined the changes of LPVRI induced by LMBO at thoracotomy. We studied a total of 13 mice pretreated with Hb, LNAME or a saline resolution 30 min right after cannulation but before LMBO. The plasma concentration of cellfree Hb enhanced from 51 mg l1 (7.9 M) at baseline to 7299 mg l1 (113 M) at 30 minutes soon after i.v. administration of Hb. Levels of metHb had been less than 1 in WB and 16 of plasma Hb at 30 minutes after the i.v. administration of Hb, maybe indicating scavenging of NO by cellfree Hb. Infusion of Hb or LNAME enhanced SAP at 30 min soon after infusion when compared to salinetreated mice (Table three).1095010-47-1 web Nitric Oxide.6-Bromo-8-iodoquinolin-2(1H)-one site Author manuscript; accessible in PMC 2014 April 01.PMID:33619166 NIHPA Author Manuscript NIHPA Author Manuscript NIHPA Author ManuscriptBeloiartsev et al.PageLMBO decreased the QLPA and elevated LPVRI without the need of affecting the HR, SAP, or PAP in mice pretreated with Hb, LNAME, or saline (Table three, Figure five). The improve of LPVRI in the course of LMBO in mice pretreated with Hb or saline was comparable. In contrast, pretreatment with LNAME resulted in a greater boost of LPVRI for the duration of LMBO as in comparison to Hbpretreated animals (Figure 5). During LMBO the arterial partial pressure of oxygen (PaO2) did not differ between mice pretreated with Hb, LNAME or saline (information not shown). Effects of NOS inhibition on superoxide generation in lung tissue The observation that in vivo pretreatment of mice with LNAME but not with plasma Hb augmented HPV indica.
