American journal of physiology. Heart and circulatory physiology
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Am. J. Physiol. Heart Circ. Physiol. · Dec 2009
RC time constant of single lung equals that of both lungs together: a study in chronic thromboembolic pulmonary hypertension.
The product of resistance, R, and compliance, C (RC time), of the entire pulmonary circulation is constant. It is unknown if this constancy holds for individual lungs. We determined R and C in individual lungs in chronic thromboembolic pulmonary hypertension (CTEPH) patients where resistances differ between both lungs. ⋯ Total RC time was 0.49+/-0.2 s, and RC times for the LF and HF lung were 0.45+/-0.2 and 0.45+/-0.1 s, respectively, not different. Proximal arterial compliance, given by the sum of main, right, and left PA compliances, was only 19% of total lung compliance. The RC time of a single lung equals that of both lungs together, and pulmonary arterial compliance comes largely from the distal vasculature.
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Am. J. Physiol. Heart Circ. Physiol. · Dec 2009
Comparative StudyMyocardial reperfusion injury management: erythropoietin compared with postconditioning.
Ischemic postconditioning (IPost) and erythropoietin (EPO) have been shown to attenuate myocardial reperfusion injury using similar signaling pathways. The aim of this study was to examine whether EPO is as effective as IPost in decreasing postischemic myocardial injury in both Langendorff-isolated-heart and in vivo ischemia-reperfusion rat models. Rat hearts were subjected to 25 min ischemia, followed by 30 min or 2 h of reperfusion in the isolated-heart study. ⋯ Second, in vivo, IPost and EPO induced an infarct size reduction compared with control (40.5+/-3.6% and 28.9+/-3.1%, respectively, vs. 53.7+/-4.3% of the area at risk; P<0.05). Again, EPO decreased significantly more infarct size and transmurality than IPost (P<0.05). In conclusion, with the use of our protocols, EPO showed better protective effects than IPost against reperfusion injury through higher phosphorylation of GSK-3beta.
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Am. J. Physiol. Heart Circ. Physiol. · Nov 2009
Comparative StudyeNOS uncoupling and endothelial dysfunction in aged vessels.
Endothelial nitric oxide synthase (eNOS) uncoupling is a mechanism that leads to endothelial dysfunction. Previously, we reported that shear stress-induced release of nitric oxide in vessels of aged rats was significantly reduced and was accompanied by increased production of superoxide (18, 27). In the present study, we investigated the influence of aging on eNOS uncoupling. ⋯ Quantitative PCR results implied that the diminished BH4 may result from the decreased expressions of GTP cyclohydrolase I and sepiapterin reductase, enzymes involved in BH4 biosynthesis. When isolated and cannulated second-order mesenteric arteries (approximately 150 microm) from aged mice were treated with sepiapterin, acetylcholine-induced, endothelium-dependent vasodilation improved significantly, which was accompanied by stabilization of the eNOS dimer. These data suggest that eNOS uncoupling and increased nitrosylation of eNOS, decreased expressions of GTP cyclohydrolase I and sepiapterin reductase, and subsequent reduced BH4 bioavailability may be important contributors of endothelial dysfunction in aged vessels.
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Am. J. Physiol. Heart Circ. Physiol. · Nov 2009
Endogenous regulation of cardiovascular function by apelin-APJ.
Studies have shown significant cardiovascular effects of exogenous apelin administration, including the potent activation of cardiac contraction. However, the role of the endogenous apelin-APJ pathway is less clear. To study the loss of endogenous apelin-APJ signaling, we generated mice lacking either the ligand (apelin) or the receptor (APJ). ⋯ Taken together, these results demonstrate that endogenous apelin-APJ signaling plays a modest role in maintaining basal cardiac function in adult mice with a more substantive role during conditions of stress. In addition, an autocrine pathway seems to exist in myocardial cells, the ablation of which reduces cellular contraction without change in calcium transient. Finally, differences in the developmental phenotype between apelin and APJ null mice suggest the possibility of undiscovered APJ ligands or ligand-independent effects of APJ.
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Am. J. Physiol. Heart Circ. Physiol. · Nov 2009
Angiotensin II enhances GABA(B) receptor-mediated responses and expression in nucleus tractus solitarii of rats.
Angiotensin II (ANG II) increases GABA(B) receptor expression in neuronal cultures from the nucleus tractus solitarii (NTS). In the present study, the chronic effects of ANG II on GABA(B) receptor expression and activity were examined in the NTS of Sprague-Dawley rats. Intracerebroventricular infusion of ANG II caused a significant elevation in blood pressure (BP) and an increase in GABA(B) receptor expression in the NTS. ⋯ In contrast, the pressor responses to the GABA(A) receptor agonist muscimol and the depressor responses to the GABA(A) receptor antagonist bicuculline were comparable between aCSF- and ANG II-infused rats. These results indicate that chronic ANG II infusion stimulates GABA(B) receptor expression and augments GABA(B) receptor-mediated responses in the NTS. This effect could contribute to the central nervous system actions of ANG II that result in dampening of baroreflexes and elevation in arterial BP.