Showing papers in "American Journal of Physiology-heart and Circulatory Physiology in 2002"
TL;DR: Aldosterone and salt treatment in uninephrectomized rats led to severe hypertension and the development of a vascular inflammatory phenotype in the heart, which may represent one mechanism by which aldosterone contributes to myocardial disease.
Abstract: Vascular inflammation was examined as a potential mechanism of aldosterone-mediated myocardial injury in uninephrectomized rats receiving 1% NaCl-0.3% KCl to drink for 1, 2, or 4 wk and 1) vehicle,...
592 citations
TL;DR: H2S is endogenously generated in vascular smooth muscle cells and the signal transduction pathways involved in the vascular effects of H2S have been unclear and were investigated.
Abstract: H2S is endogenously generated in vascular smooth muscle cells. The signal transduction pathways involved in the vascular effects of H2S have been unclear and were investigated in the present study....
484 citations
TL;DR: A new hypothesis is proposed to account for the slow oscillation in heart rate and blood pressure that incorporates components of the central nervous system, other reflex pathways regulating sympathetic activity, and resonance in the baroreflex control of blood pressure.
Abstract: Altered variability in the cardiovascular system is associated with a range of cardiovascular diseases and increased mortality. Because blood pressure and heart rate show distinct low-frequency oscillations that appear to be affected by either vagal or sympathetic activity, it has been hoped that measurement of the strength of these oscillations could be used as an index of autonomic tone and thus form the basis of a diagnostic test. This review focuses on recent research that has examined the fundamental origin of variability associated with respiration and a slow oscillation at 0.1 Hz in the human. A new hypothesis is proposed to account for the slow oscillation in heart rate and blood pressure that incorporates components of the central nervous system, other reflex pathways regulating sympathetic activity, and resonance in the baroreflex control of blood pressure. Whereas it is clear that sympathetic activity and arterial baroreflexes are critical elements in producing cardiovascular variability, there is also evidence that other factors, including the ability of the vasculature to respond to sympathetic activity, appear to play a role in determining the strength of oscillations. Given the potential impact of other nonbaroreflex or nonautonomic pathways in affecting cardiovascular variability, it is proposed that one must use care in relating changes in the strength of an oscillation in blood pressure and heart rate as definitively due to a change in autonomic control.
413 citations
TL;DR: For normal myocardium, SR(sys) reflects regional contractile function (being relatively independent of HR), whereas epsilon( sys) reflects changes in SV, as measured by stroke volume and contractility.
Abstract: For porcine myocardium, ultrasonic regional deformation parameters, systolic strain (esys) and peak systolic strain rate (SRsys), were compared with stroke volume (SV) and contractility [contractil...
397 citations
TL;DR: First evidence showing that inducible VEGF expression is sensitive to copper is presented and that the angiogenic potential of copper may be harnessed to accelerate dermal wound contraction and closure is presented.
Abstract: Angiogenesis plays a central role in wound healing. Among many known growth factors, vascular endothelial growth factor (VEGF) is believed to be the most prevalent, efficacious, and long-term signal that is known to stimulate angiogenesis in wounds. Whereas a direct role of copper to facilitate angiogenesis has been evident two decades ago, the specific targets of copper action remained unclear. This report presents first evidence showing that inducible VEGF expression is sensitive to copper and that the angiogenic potential of copper may be harnessed to accelerate dermal wound contraction and closure. At physiologically relevant concentrations, copper sulfate induced VEGF expression in primary as well as transformed human keratinocytes. Copper shared some of the pathways utilized by hypoxia to regulate VEGF expression. Topical copper sulfate accelerated closure of excisional murine dermal wound allowed to heal by secondary intention. Copper-sensitive pathways regulate key mediators of wound healing such as angiogenesis and extracellular matrix remodeling. Copper-based therapeutics represents a feasible approach to promote dermal wound healing.
393 citations
TL;DR: Results of this study show hypoxia-induced changes in paracellular permeability may be due to perturbation of TJ complexes and that posthypoxic reoxygenation reverses these effects.
Abstract: Cerebral microvessel endothelial cells that form the blood-brain barrier (BBB) have tight junctions (TJ) that are critical for maintaining brain homeostasis and low permeability. Both integral (cla...
368 citations
TL;DR: An ionic basis for APD alternans is established, which should facilitate the development of pharmacological approaches to eliminating alternans and establish a new ionic model using formulations of currents based on previous models and recent experimental data.
Abstract: Although alternans of action potential duration (APD) is a robust feature of the rapidly paced canine ventricle, currently available ionic models of cardiac myocytes do not recreate this phenomenon...
334 citations
TL;DR: In conclusion, anesthetic agent, timing of echocardiographic measurements, and genetic background are all critical variables during eChocardiography in mice.
Abstract: Anesthetics provide sedation and immobility facilitating echocardiography in mice, but influence cardiac function. We studied the effects of intraperitoneal and inhaled anesthetic agents on echocar...
332 citations
TL;DR: Comparison of results for the six different shear modes suggests that simple shear deformation is resisted by elastic elements aligned with the microstructural axes of the tissue.
Abstract: We examined the shear properties of passive ventricular myocardium in six pig hearts. Samples (3 × 3 × 3 mm) were cut from adjacent regions of the lateral left ventricular midwall, with sides align...
322 citations
TL;DR: It is concluded that the glycocalyx serves as a barrier to adhesion and that its shedding during natural activation of ECs may be an essential part of the inflammatory response.
Abstract: The binding of fluorescently labeled microspheres (FLMs, 0.1-μm diameter) coated with antibody (1a29) to ICAM-1 was studied in postcapillary venules during topical application of the chemoattractan...
313 citations
TL;DR: For the first time, it is demonstrated that sildenafil induces acute and delayed protective effects against ischemia-reperfusion injury, which are mediated by opening of mitochondrial K(ATP) channels.
Abstract: Sildenafil citrate (Viagra) is the pharmacological agent used to treat erectile dysfunction in men. Because this drug has a vasodilatory effect, we hypothesized that such an action may induce a pre...
TL;DR: A functional link between the monocyte concentration in the peripheral blood and the enhancement of arteriogenesis is demonstrated, demonstrated by laser-Doppler imaging before and at various time points after surgery.
Abstract: 0.1152/ajpheart. 01098.2001.—Arteriogenesis has been associated with the presence of monocytes/macrophages within the collateral vessel wall. We tested the hypothesis that arteriogenesis is functio...
TL;DR: A beta disrupts a critical homeostatic mechanism of the cerebral circulation and renders CBF highly dependent on MAP, and may play a role in the brain dysfunction and periventricular white-matter changes associated with Alzheimer's dementia.
Abstract: The amyloid-β (Aβ) peptide, which is derived from the amyloid precursor protein (APP), is involved in the pathogenesis of Alzheimer's dementia and impairs endothelium-dependent vasodilation in cere...
TL;DR: Transforming growth factor-β1 promotes or inhibits cell proliferation and induces fibrotic processes and extracellular matrix production in numerous cell types.
Abstract: Transforming growth factor-β1 (TGF-β1) promotes or inhibits cell proliferation and induces fibrotic processes and extracellular matrix production in numerous cell types. Several cardiac diseases ar...
TL;DR: A physiological oscillator model of which the output mimics the shape of the R-R interval Poincaré plot is developed, which provides a theoretical link between frequency-domain spectral analysis techniques and time-domain Poinceré plot analysis.
Abstract: In this paper, we develop a physiological oscillator model of which the output mimics the shape of the R-R interval Poincare plot. To validate the model, simulations of various nervous conditions are compared with heart rate variability (HRV) data obtained from subjects under each prescribed condition. For a variety of sympathovagal balances, our model generates Poincare plots that undergo alterations strongly resembling those of actual R-R intervals. By exploiting the oscillator basis of our model, we detail the way that low- and high-frequency modulation of the sinus node translates into R-R interval Poincare plot shape by way of simulations and analytic results. With the use of our model, we establish that the length and width of a Poincare plot are a weighted combination of low- and high-frequency power. This provides a theoretical link between frequency-domain spectral analysis techniques and time-domain Poincare plot analysis. We ascertain the degree to which these principles apply to real R-R intervals by testing the mathematical relationships on a set of data and establish that the principles are clearly evident in actual HRV records.
TL;DR: Cardiac function was normalized in transgenic db/ db-hGLUT4 mice, indicating that altered cardiac metabolism can produce contractile dysfunction in diabetic db/db hearts.
Abstract: Control db/+ and diabeticdb/db mice at 6 and 12 wk of age were subjected to echocardiography to determine whether contractile function was reduced in vivo and restored in transgenicdb/db-human gluc...
TL;DR: Using a 24-h rat cecal ligation and perforation model of sepsis, a profound maldistribution of microvascular blood flow is studied and O2 transp...
Abstract: Inherent in the remote organ injury caused by sepsis is a profound maldistribution of microvascular blood flow. Using a 24-h rat cecal ligation and perforation model of sepsis, we studied O2 transp...
TL;DR: It is indicated that HF remodels electrophysiology in all layers of the left ventricle, and the downregulation of I(K1), I(to1), and I(ks) increases APD and favors occurrence of EADs.
Abstract: Heart failure (HF) produces important alterations in currents underlying cardiac repolarization, but the transmural distribution of such changes is unknown. We therefore recorded action potentials ...
TL;DR: It is indicated that aging impairs vasodilatory responses mediated through the endothelium of resistance arterioles from locomotory muscle, whereas smooth muscle vasodILatory responses remain intact with aging.
Abstract: Blood flow capacity in skeletal muscle declines with age. Reduced blood flow capacity may be related to decline in the maximal vasodilatory capacity of the resistance vasculature. This study tested the hypothesis that aging results in impaired vasodilatory capacity of first-order (1A) arterioles isolated from rat-hindlimb locomotory muscle: 1A arterioles (90-220 microm) from gastrocnemius and soleus muscles of young (4 mo) and aged (24 mo) Fischer-144 rats were isolated, cannulated, and pressurized via hydrostatic reservoirs. Vasodilatory responses to increasing concentrations of ACh (10(-9) to 10(-4) M), adenosine (ADO, 10(-10) to 10(-4) M), and sodium nitroprusside (SNP, 10(-10) to 10(-4) M) were evaluated at a constant intraluminal pressure of 60 cmH(2)O in the absence of flow. Flow-induced vasodilation was also evaluated in the absence of pressure changes. Responses to ADO and SNP were not altered by age. Endothelium-dependent vasodilation induced by flow was significantly reduced in arterioles from both gastrocnemius and soleus muscles. In contrast, endothelium-dependent vasodilation to ACh was reduced only in soleus muscle arterioles. These results indicate that aging impairs vasodilatory responses mediated through the endothelium of resistance arterioles from locomotory muscle, whereas smooth muscle vasodilatory responses remain intact with aging. Additionally, ACh-induced vasodilation was altered by age only in soleus muscle arterioles, suggesting that the mechanism of age-related endothelial impairment differs in arterioles from soleus and gastrocnemius muscles.
TL;DR: The goal of the study was to determine whether defects in intracellular Ca2+ signaling contribute to cardiomyopathy in streptozotocin (STZ)-induced diabetic rats.
Abstract: The goal of the study was to determine whether defects in intracellular Ca2+ signaling contribute to cardiomyopathy in streptozotocin (STZ)-induced diabetic rats. Depression in cardiac systolic and...
TL;DR: It is shown that diazoxide pretreatment preserves the normal low outer membrane permeability to nucleotides and cytochrome c and that these beneficial effects are abolished by the mitoK(ATP) channel inhibitor 5-hydroxydecanoate.
Abstract: Diazoxide opening of the mitochondrial ATP-sensitive K+ (mitoKATP) channel protects the heart against ischemia-reperfusion injury by unknown mechanisms. We investigated the mechanisms by which mito...
TL;DR: Mild endovascular cooling to 34 degrees C lowers myocardial temperature sufficiently in human-sized hearts to cause a substantial cardioprotective effect, preserve microvascular flow, and maintain cardiac output in hypothermic hearts.
Abstract: Mild hypothermia reduces myocardial infarct size in small animals; however, the extent of myocardial protection in large animals with greater thermal mass remains unknown. We evaluated the effects ...
TL;DR: The results suggest that shear stress stimulates eNOS by two different mechanisms: 1) PKA- and PI3K-dependent and 2) Pka-dependent but PI3k-independent pathways.
Abstract: Shear stress stimulates nitric oxide (NO) production by phosphorylating endothelial NO synthase (eNOS) at Ser(1179) in a phosphoinositide-3-kinase (PI3K)- and protein kinase A (PKA)-dependent manner. The eNOS has additional potential phosphorylation sites, including Ser(116), Thr(497), and Ser(635). Here, we studied these potential phosphorylation sites in response to shear, vascular endothelial growth factor (VEGF), and 8-bromocAMP (8-BRcAMP) in bovine aortic endothelial cells (BAEC). All three stimuli induced phosphorylation of eNOS at Ser(635), which was consistently slower than that at Ser(1179). Thr(497) was rapidly dephosphorylated by 8-BRcAMP but not by shear and VEGF. None of the stimuli phosphorylated Ser(116). Whereas shear-stimulated Ser(635) phosphorylation was not affected by phosphoinositide-3-kinase inhibitors wortmannin and LY-294002, it was blocked by either treating the cells with a PKA inhibitor H89 or infecting them with a recombinant adenovirus-expressing PKA inhibitor. These results suggest that shear stress stimulates eNOS by two different mechanisms: 1) PKA- and PI3K-dependent and 2) PKA-dependent but PI3K-independent pathways. Phosphorylation of Ser(635) may play an important role in chronic regulation of eNOS in response to mechanical and humoral stimuli.
TL;DR: It is concluded that LV hypertrophy in normotensive and preeclamptic pregnancy matches changes in cardiac work, and LV contractility is preserved.
Abstract: Increased cardiac output in pregnancy is associated with cardiac remodeling and possible reduction in contractility, which may worsen in preeclampsia. Left ventricular (LV) geometry and function we...
TL;DR: The transmural course of the helix angle corresponded to data reported in literature and appeared to be <0.07 mm(-1) throughout the myocardial walls except for the fusion sites between the left and right ventricles and the insertion sites of the papillary muscles.
Abstract: Cardiac myofiber orientation is a crucial determinant of the distribution of myocardial wall stress. Myofiber orientation is commonly quantified by helix and transverse angles. Accuracy of reported...
TL;DR: The QT-RR relationship exhibits substantial intersubject variability as well as a high intrasubject stability, which has practical implications for a precise estimation of the heart rate-corrected QT interval in which optimized subject-specific rate correction formulas should be used.
Abstract: Recently, it was demonstrated that the QT-RR relationship pattern varies significantly among healthy individuals. We compared the intra- and interindividual variations of the QT-RR relationship. Tw...
TL;DR: It is demonstrated that resveratrol can pharmacologically precondition the heart in a NO-dependent manner and provided cardioprotection as evidenced by improved postischemic ventricular functional recovery and reduced myocardial infarct size and cardiomyocyte apoptosis.
Abstract: Resveratrol (trans-3,4′,5-trihydroxystilbene), a recently described grape-derived polyphenolic antioxidant, has been found to protect the heart from ischemic-reperfusion injury. The present study s...
TL;DR: The cardioprotecive mechanism of K(+)-free channel openers includes direct attenuation of mitochondrial oxidant stress at reoxygenation, suggesting the existence of a K(+) conductance-independent pathway for mitochondrial protection targeted by K(+.
Abstract: K+ channel openers have been recently recognized for their ability to protect mitochondria from anoxic injury. Yet the mechanism responsible for mitochondrial preservation under oxidative stress is...
TL;DR: Evidence is provided that Provinol accelerates the regression of blood pressure and improves structural and functional cardiovascular changes produced by chronic inhibition of NO synthesis.
Abstract: The effects of the red wine polyphenolic compounds (Provinol) on hypertension, left ventricular hypertrophy, myocardial fibrosis, and vascular remodeling were investigated after chronic inhibition ...
TL;DR: An improved mathematical model for a single primary pacemaker cell of the rabbit sinoatrial node that can simulate whole cell voltage-clamp data for I(Ca,L), I(Kr), and I(st) and mimic the effects of channel blockers or Ca(2+) buffers on pacemaker activity more accurately than the previous models is developed.
Abstract: We developed an improved mathematical model for a single primary pacemaker cell of the rabbit sinoatrial node. Original features of our model include 1) incorporation of the sustained inward curren...