Impaired NO-mediated vasodilation with increased superoxide but robust EDHF function in right ventricular arterial microvessels of pulmonary hypertensive rats

Abstract

Impaired NO-mediated vasodilation with increased superoxide but robust EDHF function in right ventricular arterial microvessels of pulmonary hypertensive rats. Am J Physiol Heart Circ Physiol 292: H2737-H2744, 2007. First published January 12, 2007; doi:10.1152/ajpheart.00548.2006.-Pulmonary hypertension (PH) causes right ventricular (RV) hypertrophy and, according to the extent of pressure overload, eventual heart failure. We tested the hypothesis that the mechanical stress in PH-RV impairs the vasoreactivity of the RV coronary microvessels of different sizes with increased superoxide levels. Five-week-old male Sprague-Dawley rats were injected with monocrotaline (n ϭ 126) to induce PH or with saline as controls (n ϭ 114). After 3 wk, coronary arterioles (diameter ϭ 30 -100 m) and small arteries (diameter ϭ 100 -200 m) in the RV were visualized using intravital videomicroscopy. We evaluated ACh-induced vasodilation alone, in the presence of N -nitro-Larginine methyl ester (L-NAME), in the presence of tetraethylammonium (TEA) or catalase with or without L-NAME, and in the presence of SOD. The degree of suppression in vasodilation by L-NAME and TEA was used as indexes of the contributions of endothelial nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF), respectively. In PH rats, ACh-induced vasodilation was significantly attenuated in both arterioles and small aretries, especially in arterioles. This decreased vasodilation was largely attributable to reduced NOmediated vasoreactivity, whereas the EDHF-mediated vasodilation was relatively robust. The suppressive effect on arteriolar vasodilation by catalase was similar to TEA in both groups. Superoxide, as measured by lucigenin chemiluminescence, was significantly elevated in the RV tissues in PH. SOD significantly ameliorated the impairment of ACh-induced vasodilation in PH. Robust EDHF function will play a protective role in preserving coronary microvascular homeostasis in the event of NO dysfunction with increased superoxide levels. acetylcholine; N -nitro-L-arginine methyl ester; tetraethylanmonium; catalase; superoxide dimutase; endothelium-derived hyperpolarizing factor PULMONARY HYPERTENSION (PH) causes pressure overload and hypertrophy, finally leading to failure, in the right ventricle (RV) of the heart. Although the right coronary perfusion pressure remains relatively unchanged, the high pressure and hypertrophy of the RV affect the coronary hemodynamics (8, 13), and patients with PH and RV hypertrophy might have symptoms indistinguishable from those of angina pectoris (4, 30). In chronic PH, coronary flow regulation is the only mechanism that maintains the oxygen supply to the RV, since no further increase in the absorption of oxygen is possible (31). The endothelium-dependent vasodilation of coronary small arteries (SAs, diameter ϭ 100 -200 m) isolated from the RV has been shown to be lower in rats with chronic PH (33), whereas in acute PH, endogenous nitric oxide (NO) regulates right coronary blood flow (37). However, the contri...

In vivo characterization of rodent cyclic myocardial perfusion variation at rest and during adenosine-induced stress using cine-ASL cardiovascular magnetic resonance

“…Left-coronary arterial blood flow is characterized by a diastolic-dominant inflow [35] whereas small distal venous flow exhibits a systolic-dominant pattern [36]. Our results are consistent with the expected physiological pattern of preferential coronary diastolic filling.…”

Effects of propionyl-L-carnitine on ischemia–reperfusion injury in hamster cheek pouch microcirculation

“…Previous data indicate that pLc improves arterial perfusion (Alvarez de Sotomayor et al, 2007). The effects on arterial diameter likely due to preserved NO and EDHF release, as shown also by Kajiya et al (2007) and Karmakar (2001) and the reduction of E-selectin expression, may be the basis for increased capillary perfusion and capillary RBC velocity as indicated by our results.…”

The Right Ventricle Under Pressure

“…59 Finally, RV ischemia in pulmonary hypertension may ensue due to a decreased NO-mediated vasodilation of RV small arteries, which seems related to increased superoxide production. 60 …”