Angiotensin II induces carbon monoxide production in isolated rat kidney

Abstract

P106 Chronic angiotensin II (Ang II) infusion induces vascular expression of heme oxygenase (HO)-1. HO-dependent synthesis of carbon monoxide (CO) subserves vasodilatory mechanisms. We examined whether Ang II stimulates CO production in isolated rat kidneys perfused at 7 ml/min with oxygenated Krebs buffer. We monitored perfusion pressure (PP) continuously and measured the concentration of CO in the renal venous effluent by gas chromatography/mass spectroscopy. At the conclusion of perfusion for 120 min after the onset of treatment with Ang II or vehicle, the kidneys were processed for measurement of HO activity and isoform expression. In control experiment without experimental interventions, PP and concentration of CO in the venous effluent remained stable throughout the perfusion, ranging between 78 ± 7.7 and 83 ± 5.5, mmHg and 12.3 ± 5.7 and 15.1 ± 6.6 nM, respectively. Inclusion of Ang II (1μM) into the perfusion increased PP by 31.5 ± 14, 43.5 ± 14.5, 47 ± 13, 53 ± 11.2, after 30, 60,90,120 min, respectively. Ang II also increased (p 1 receptor antagonist, losartan (1 μM) or protein kinase C (PKC) inhibitor, staurosporine (100nM). HO activity in control kidneys (111.03 ± 2.25, pmol/mg/4h) was exceeded by HO activity in kidneys perfused with Ang II (162.40 ± 6.95, p