Genetic background influences arterial vasomotor function in male and female mice.

The purpose of this study was to assess the influence of genetic background and sex on nitric oxide (NO)-mediated vasomotor function in arteries from different vascular territories. Vasomotor function was assessed in thoracic aorta, abdominal aorta, carotid arteries, and femoral arteries from the following mouse strains: SJL/J, DBA/2J, NZW/LacJ, and C57BL/6J. Contractile responses were assessed using the α1-adrenergic receptor agonist phenylephrine (PE, 10 -10  M).

Age-Associated Dysregulation of Integrin Function in Vascular Smooth Muscle.

Arterial aging results in a progressive reduction in elasticity of the vessel wall and an impaired ability of aged blood vessels to control local blood flow and pressure. Recently, a new concept has emerged that the stiffness and decreased contractility of vascular smooth muscle (VSM) cells are important contributors to age-induced arterial dysfunction. This study investigated the hypothesis that aging alters integrin function in a matrix stiffness-dependent manner, which contributes to decreased VSM contractility in aged soleus muscle feed arteries (SFA).

Applications and strategies in nanodiagnosis and nanotherapy in lung cancer.

Lung cancer is the second most common cancer and the leading cause of death in both men and women in the world. Lung cancer is heterogeneous in nature and diagnosis is often at an advanced stage as it develops silently in the lung and is frequently associated with high mortality rates. Despite the advances made in understanding the biology of lung cancer, progress in early diagnosis, cancer therapy modalities and considering the mechanisms of drug resistance, the prognosis and outcome still remains low for many patients.

Heterogeneous effect of aging on vasorelaxation responses in large and small arteries.

Aging is associated with impaired vascular function characterized in part by attenuated vasorelaxation to acetylcholine (ACh) and sodium nitroprusside (SNP). Due to structural and functional differences between conduit and resistance arteries, the effect of aging on vasorelaxation responses may vary along the arterial tree. Our purpose was to determine age-related differences in vasorelaxation responses in large and small arteries.

Vascular smooth muscle stiffness and its role in aging.

Vascular smooth muscle cells (VSMC) are now considered important contributors to the pathophysiological and biophysical mechanisms underlying arterial stiffening in aging. Here, we review mechanisms whereby VSMC stiffening alters vascular function and contributes to the changes in vascular stiffening observed in aging and cardiovascular disease. Vascular stiffening in arterial aging was historically associated with changes in the extracellular matrix; however, new evidence suggests that endothelial and vascular smooth muscle cell stiffness also contribute to overall blood vessel stiffness.

Vascular Smooth Muscle Contractile Function Declines With Age in Skeletal Muscle Feed Arteries.

Aging induces a progressive decline in vasoconstrictor responses in central and peripheral arteries. This study investigated the hypothesis that vascular smooth muscle (VSM) contractile function declines with age in soleus muscle feed arteries (SFA). Contractile function of cannulated SFA isolated from young (4 months) and old (24 months) Fischer 344 rats was assessed by measuring constrictor responses of denuded (endothelium removed) SFA to norepinephrine (NE), phenylephrine (PE), and angiotensin II (Ang II).

Importance of mechanical signals in promoting exercise-induced improvements in vasomotor function of aged skeletal muscle resistance arteries.

Current research indicates that vasomotor responses are altered with aging in skeletal muscle resistance arteries. The changes in vasomotor function are characterized by impaired vasodilator and vasoconstrictor responses. The detrimental effects of aging on vasomotor function are attenuated in some vascular beds after a program of endurance exercise training.

An Acute Bout of Aquatic Treadmill Exercise Induces Greater Improvements in Endothelial Function and Postexercise Hypotension Than Land Treadmill Exercise: A Crossover Study.

Objective: The purpose of the study was to compare acute bouts of aquatic treadmill (ATM) and land treadmill (LTM) exercise on flow-mediated dilation, postexercise blood pressure, plasma nitrate/nitrite, and atrial natriuretic peptide in untrained, prehypertensive men.

Design: In a counterbalanced, crossover design, 19 untrained, prehypertensive men completed bouts of ATM and LTM on separate days. Flow-mediated dilation was measured pre-exercise and 1-hr postexercise.

Short-term increases in pressure and shear stress attenuate age-related declines in endothelial function in skeletal muscle feed arteries.

Purpose: We tested the hypothesis that exposure to a short-term (1 h) increase in intraluminal pressure and shear stress (SS), to mimic two mechanical signals associated with a bout of exercise, improves nitric oxide (NO)-mediated endothelium-dependent dilation in aged soleus muscle feed arteries (SFA). In addition, we hypothesized that pressure and SS would interact to produce greater improvements in endothelial function than pressure alone.

Methods: SFA from young (4 months) and old (24 months) Fischer 344 rats were cannulated and pressurized at 90 (P90) or 130 (P130) cmH2O and exposed to no SS (0 dyn/cm(2)) or high SS (~65 dyn/cm(2)) for 1 h.

Short-duration increases in intraluminal pressure improve vasoconstrictor responses in aged skeletal muscle feed arteries.

Purpose: We tested the hypothesis that exposure to a short-duration (1 h) increase in intraluminal pressure, to mimic pressure associated with a bout of exercise, would attenuate age-induced impairments of vascular smooth muscle (VSM) constrictor responses in soleus muscle feed arteries (SFA) via the Rho pathway.

Methods: SFA from young (4 months) and old (24 months) Fischer 344 rats were cannulated and pressurized to 90 or 130 cmH2O for 1 h. Following the 1-h treatment, pressure in P130 arteries was lowered to 90 cmH2O for examination of vasoconstrictor responses to norepinephrine (NE), angiotensin II (Ang II), and phenylephrine (PE).

Acute increases in intraluminal pressure improve vasodilator responses in aged soleus muscle feed arteries.

Purpose: We tested the hypothesis that exposure to an acute increase in intraluminal pressure, to mimic pressure associated with a bout of exercise, improves nitric oxide (NO)-mediated endothelium-dependent dilation in aged soleus muscle feed arteries (SFA) and that improved endothelial function would persist after a 2 h recovery period.

Methods: SFA from young (4-month) and old (24-month) Fischer 344 rats were cannulated and pressurized at 90 (P90) or 130 (P130) cmH2O for 60 min. At the end of the treatment period, pressure in the P130 SFA was lowered to 90 cmH2O for examination of endothelium-dependent [flow or acetylcholine (ACh)] and endothelium-independent [sodium nitroprusside (SNP)] vasodilation.

Effect of age and exercise training on protein:protein interactions among eNOS and its regulatory proteins in rat aortas.

Purpose: We tested the hypothesis that impaired endothelium-dependent relaxation in aged aorta is due, in part, to altered protein:protein interactions between endothelial nitric oxide synthase (eNOS) and key regulatory proteins resulting in impaired nitric oxide (NO)-mediated relaxation. We also hypothesized that endurance exercise training improves or restores NO-mediated vasorelaxation in aged aorta by reversing the detrimental effects of aging on protein:protein interaction between eNOS and its key regulatory proteins.

Methods: Young (2 month) and old (22 month) rats were exercise trained (Ex) or remained sedentary (Sed) for 10 weeks yielding four groups of rats: (1) young Sed, (2) young Ex, (3) old Sed, and (4) old Ex.

Aging impairs PI3K/Akt signaling and NO-mediated dilation in soleus muscle feed arteries.

We tested the hypothesis that impaired nitric oxide (NO)-mediated, endothelium-dependent dilation in aged soleus muscle feed arteries (SFA) is due to an age-related decline in the potential for PI3-kinase (PI3K)/protein kinase B (Akt)-dependent phosphorylation of endothelial NO synthase (eNOS) on serine residue 1177 (p-eNOS(ser1177)). SFA from young (4 months) and old (24 months) Fischer 344 rats were cannulated for examination of endothelium-dependent [flow or acetylcholine (ACh)] and endothelium-independent [sodium nitroprusside (SNP)] vasodilator function. To determine the mechanism by which aging affected vasodilation to flow and ACh, vasodilator responses were assessed in the presence of N (ω)-nitro-L-arginine (L-NNA, to inhibit NOS), LY-294002 (to inhibit PI3K), or 1L6-hydroxymethyl-chiro-inositol-2-(R)-2-O-methyl-3-O-octadecyl-sn-glycerocarbonate (AktI, to inhibit Akt).

NAD(P)H oxidase-derived reactive oxygen species contribute to age-related impairments of endothelium-dependent dilation in rat soleus feed arteries.

We tested the hypothesis that age-related endothelial dysfunction in rat soleus muscle feed arteries (SFA) is mediated in part by NAD(P)H oxidase-derived reactive oxygen species (ROS). SFA from young (4 mo) and old (24 mo) Fischer 344 rats were isolated and cannulated for examination of vasodilator responses to flow and acetylcholine (ACh) in the absence or presence of a superoxide anion (O(2)(-)) scavenger (Tempol; 100 μM) or an NAD(P)H oxidase inhibitor (apocynin; 100 μM). In the absence of inhibitors, flow- and ACh-induced dilations were attenuated in SFA from old rats compared with young rats.

Exercise training reverses age-related decrements in endothelium-dependent dilation in skeletal muscle feed arteries.

We tested two hypotheses, first that exercise training reverses age-related decrements in endothelium-dependent dilation in soleus muscle feed arteries and second that this improved endothelium-dependent dilation is the result of increased nitric oxide (NO) bioavailability due to increased content and phosphorylation of endothelial NO synthase (eNOS) and/or increased antioxidant enzyme content. Young (2 mo) and old (22 mo) male Fischer 344 rats were exercise trained (Ex) or remained sedentary (Sed) for 10-12 wk, yielding four groups of rats: 1) young Sed (4-5 mo), 2) young Ex (4-5 mo), 3) old Sed (24-25 mo), and 4) old Ex (24-25 mo). Soleus muscle feed arteries (SFA) were isolated and cannulated with two glass micropipettes for examination of endothelium-dependent (ACh) and endothelium-independent [sodium nitroprusside (SNP)] vasodilator function.

Decreased NO signaling leads to enhanced vasoconstrictor responsiveness in skeletal muscle arterioles of the ZDF rat prior to overt diabetes and hypertension.

Approximately 40% of patients with type 2 diabetes present with concurrent hypertension at the time of diabetes diagnosis. Increases in peripheral vascular resistance and correspondingly enhanced vasoconstrictor capacity could have profound implications for the development of hypertension and the progression of insulin resistance to overt diabetes. The purpose of this study was to determine whether skeletal muscle arteriolar vasoconstrictor dysfunction precedes or occurs concurrently with the onset of diabetes and hypertension.

Short-term increases in intraluminal pressure reverse age-related decrements in endothelium-dependent dilation in soleus muscle feed arteries.

We tested the hypothesis that short-term increases in intraluminal pressure improve endothelium-dependent dilation and increase endothelial nitric oxide (NO) synthase (eNOS) expression in senescent soleus muscle feed arteries (SFA). SFA isolated from young (4 mo) and old (24 mo) Fischer 344 rats were cannulated and pressurized at 90 (p90) or 130 (p130) cmH(2)O for 4 h. At the end of the 4-h protocol, pressure in p130 SFA was lowered to 90 cmH(2)O for examination of endothelium-dependent (flow- or ACh-induced) vasodilation.

Exercise training improves femoral artery blood flow responses to endothelium-dependent dilators in hypercholesterolemic pigs.

We tested two hypotheses: 1) that the effects of hypercholesterolemia on endothelial function in femoral arteries exceed those reported in brachial arteries and 2) that exercise (Ex) training enhances endothelium-dependent dilation and improves femoral artery blood flow (FABF) in hypercholesterolemic pigs. Adult male pigs were fed a normal fat (NF) or high-fat/cholesterol (HF) diet for 20 wk. Four weeks after the diet was initiated, pigs were Ex trained or remained sedentary (Sed) for 16 wk, thus yielding four groups: NF-Sed, NF-Ex, HF-Sed, and HF-Ex.

Endurance exercise training improves endothelium-dependent relaxation in brachial arteries from hypercholesterolemic male pigs.

We tested the hypothesis that exercise (Ex) training attenuates hypercholesterolemia-induced impairment of endothelium-dependent relaxation (EDR) in brachial (Br) arteries of adult male pigs by enhancing nitric oxide (NO)-mediated EDR. Adult male pigs were fed a normal-fat (NF) or high-fat/cholesterol (HF) diet for 20 wk. Four weeks after the diet was initiated, pigs were trained or remained sedentary (Sed) for 16 wk, yielding four groups: 1) NF-Sed, 2) NF-Ex, 3) HF-Sed, and 4) HF-Ex.

Shear stress induces eNOS mRNA expression and improves endothelium-dependent dilation in senescent soleus muscle feed arteries.

We tested the hypothesis that increased intraluminal shear stress induces endothelial nitric oxide (NO) synthase (eNOS) mRNA expression and improves endothelium-dependent dilation in senescent soleus muscle feed arteries (SFA) by increasing NO production. SFA were isolated from young (4 mo) and old (24 mo) male Fischer 344 rats and cannulated with two resistance-matched glass micropipettes. SFA were exposed to no flow (NF), low flow (LF), intermediate flow (IF), or high flow (HF) for 4 h.

Exercise preserves endothelium-dependent relaxation in coronary arteries of hypercholesterolemic male pigs.

We tested the hypothesis that exercise training (Ex) attenuates hypercholesterolemia-induced impairment of endothelium-dependent relaxation (EDR) in male porcine coronary arteries [left anterior descending coronary arteries (LAD)] by increasing nitric oxide (NO) release [due to increased endothelial NO synthase (NOS) expression] and/or increased bioactivity of NO. Adult male pigs were fed a normal-fat (NF) or high-fat (HF) diet for 20-24 wk. Pigs were Ex or remained sedentary (Sed) for 16-20 wk, beginning after 4 wk on diet.

Exercise attenuates the effects of hypercholesterolemia on endothelium-dependent relaxation in coronary arteries from adult female pigs.

We tested the hypothesis that exercise training (Ex) attenuates the effects of hypercholesterolemia on endothelium-dependent relaxation in left anterior descending coronary arteries. Adult female pigs were fed a normal-fat (NF) or high-fat (HF) diet for 20 wk. Four weeks after the diet was initiated, pigs were trained or remained sedentary (Sed) for 16 wk, yielding four groups of pigs: 1) NF-Sed, 2) NF-Ex, 3) HF-Sed, and 4) HF-Ex.

Selected Contribution: Aging impairs nitric oxide and prostacyclin mediation of endothelium-dependent dilation in soleus feed arteries.

We tested the hypothesis that endothelium-dependent dilation in soleus muscle feed arteries (SFA) is impaired by aging due to attenuated nitric oxide (NO)-mediated vasodilation. SFA were isolated from young (4 mo) and old (24 mo) male Fischer 344 rats and cannulated with two glass micropipettes for examination of endothelium-dependent [flow or acetylcholine (ACh)] and endothelium-independent [sodium nitroprusside (SNP)] vasodilator function. Flow- and ACh-induced dilation was significantly attenuated by age, whereas dilation to SNP was not compromised.

Exercise training preserves endothelium-dependent relaxation in brachial arteries from hyperlipidemic pigs.

We tested the hypothesis that exercise training (Ex) attenuates the effects of hyperlipidemia on endothelial function by enhancing NO-mediated vasorelaxation in porcine brachial (Br) arteries. Adult female pigs were fed a normal-fat (NF) or high-fat (HF) diet for 20 wk. Four weeks after initiation of the diet, pigs underwent Ex or remained sedentary (Sed) for 16 wk.