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American Journal of Physiology. Heart... Aug 2014The incidence of cardiovascular disease increases progressively with age, but aging may affect men and women differently. Age-associated changes in vascular structure...
The incidence of cardiovascular disease increases progressively with age, but aging may affect men and women differently. Age-associated changes in vascular structure and function may manifest in impaired nutritive blood flow, although the regulation of nutritive blood flow in healthy aging is not well understood. The purpose of this study was to determine if nitric oxide (NO)-mediated or α-adrenergic-mediated regulation of nutritive skeletal muscle blood flow is impaired with advanced age, and if exercise training improves age-related deficiencies. Nutritive blood flow was monitored in the vastus lateralis of healthy young and aged men and women via the microdialysis-ethanol technique prior to and following seven consecutive days of exercise training. NO-mediated and α-adrenergic-mediated regulation of nutritive blood flow was assessed by microdialysis perfusion of acetylcholine, sodium nitroprusside, N(G)-monomethyl-L-arginine, norepinephrine, or phentolamine. Pretraining nutritive blood flow was attenuated in aged compared with young women (7.39 ± 1.5 vs. 15.5 ± 1.9 ml·100 g(−1)·min(−1), P = 0.018), but not aged men (aged 13.5 ± 3.7 vs. young 9.4 ± 1.3 ml·100 g(−1)·min(−1), P = 0.747). There were no age-associated differences in NO-mediated or α-adrenergic-mediated nutritive blood flow. Exercise training increased resting nutritive blood flow only in young men (9.4 ± 1.3 vs. 19.7 ml·100 g(−1)·min(−1), P = 0.005). The vasodilatory effect of phentolamine was significantly reduced following exercise training only in young men (12.3 ± 6.14 vs. −3.68 ± 3.26 ml·100 g(−1)·min(−1), P = 0.048). In conclusion, the age-associated attenuation of resting nutritive skeletal muscle blood flow was specific to women, while the exercise-induced alleviation of α-adrenergic mediated vasoconstriction that was specific to young men suggests an age-associated modulation of the sympathetic response to exercise training.
Topics: Acetylcholine; Adrenergic alpha-Agonists; Adrenergic alpha-Antagonists; Adult; Aged; Aging; Enzyme Inhibitors; Exercise; Female; Humans; Male; Middle Aged; Muscle, Skeletal; Nitric Oxide Donors; Nitroprusside; Norepinephrine; Phentolamine; Regional Blood Flow; Sex Factors; Vasoconstriction; Vasodilator Agents; omega-N-Methylarginine
PubMed: 24951753
DOI: 10.1152/ajpheart.00247.2014 -
British Journal of Clinical Pharmacology Oct 2014A major feature of endothelial dysfunction is reduced endothelium-dependent vasodilation, which in ageing may be due to decreased production of endothelial prostacyclin,...
AIM
A major feature of endothelial dysfunction is reduced endothelium-dependent vasodilation, which in ageing may be due to decreased production of endothelial prostacyclin, or nitric oxide (NO), or both.
METHOD
We tested this hypothesis in 12 younger (age 18-38 years, six women) and 12 older healthy adults (age 55-73 years, six post-menopausal women). Endothelium-dependent vasodilation was assessed by the forearm vascular conductance (FVC) response to intra-arterial acetylcholine (ACh) (0.5, 1.0, 2.0, 4.0 μg dl(-1) forearm tissue min(-1) ) before and 90 min after inhibition of the enzyme cyclo-oxygenase-2 (COX-2) with oral celecoxib (400 mg), followed by the addition of endothelial NO synthase inhibition with intra-arterial N(G) -monomethyl-l arginine acetate (L-NMMA).
RESULTS
Ageing was associated with a significantly reduced FVC response to ACh (P = 0.009, age-by-dose interaction; highest dose FVC ± SEM in ageing: 11.2 ± 1.4 vs. younger: 17.7 ± 2.4 units, P = 0.02). Celecoxib did not reduce resting FVC or the responses to ACh in any group. L-NMMA significantly reduced resting FVC and the responses to ACh in all groups, and absolute FVC values following L-NMMA were similar between groups.
CONCLUSION
In healthy normotensive younger and older adults, there is minimal contribution of prostacyclin to ACh-mediated vasodilation, yet the NO component of vasodilation is reduced with ageing. In the clinical context, these findings suggest that acute administration of medications that inhibit prostacyclin (i.e. COX-2 inhibitors) evoke modest vascular consequences in healthy persons. Additional studies are necessary to test whether chronic use of COX-2 medications reduces endothelium dependent vasodilation in older persons with or without cardiovascular risk factors.
Topics: Acetylcholine; Adolescent; Adult; Age Factors; Aged; Cyclooxygenase 2 Inhibitors; Endothelium, Vascular; Female; Humans; Male; Middle Aged; Nitric Oxide; Vasodilation; Young Adult; omega-N-Methylarginine
PubMed: 24698105
DOI: 10.1111/bcp.12397 -
British Journal of Clinical Pharmacology Oct 2014Clinical trials suggest that statins have beneficial effects on the cardiovascular system independent from their cholesterol lowering properties. In patients with... (Randomized Controlled Trial)
Randomized Controlled Trial
AIMS
Clinical trials suggest that statins have beneficial effects on the cardiovascular system independent from their cholesterol lowering properties. In patients with chronic kidney disease stage II-III, we tested the hypothesis that atorvastatin increased systemic and renal nitric oxide (NO) availability using L-N(G) -monomethyl arginine (L-NMMA) as an inhibitor of NO production.
METHODS
In a randomized, placebo-controlled, crossover study patients were treated with atorvastatin for 5 days with standardized diet and fluid intake. Glomerular filtration reate (GFR), fractional excretions of sodium (FENa ), urinary excretion of aquaporin-2 (u-AQP2) and epithelial sodium channels (u-ENaCγ ), vasoactive hormones (renin, angiotensin II, aldosterone, arginine vasopressin, endothelin-1 and brain natriuretic peptide) and central blood pressure (BP) estimated by applanation tonometry were measured before and after systemic administration of the NO inhibitor L-NMMA.
RESULTS
Atorvastatin caused a significant reduction in U-ENaCγ , but sodium excretion, C H 2 O , FENa and u-AQP2 were not changed by atorvastatin. L-NMMA reduced renal effect variables, including GFR, FENa and u-ENaCγ and increased brachial BP and central BP to a similar extent during both treatments. Vasoactive hormones were changed in the same way by L-NMMA during atorvastatin and placebo treatment.
CONCLUSION
During, atorvastatin and placebo treatment, inhibition of nitric oxide synthesis induced the same response in brachial and central blood pressure, GFR, renal tubular function and vasoactive hormones. Thus, the data do not support that atorvastatin changes nitric oxide availability in patients with mild nephropathy. The reduced u-ENaC may reflect changes in sodium absorption in the nephron induced by atorvastatin.
Topics: Adult; Aged; Aged, 80 and over; Atorvastatin; Blood Pressure; Cross-Over Studies; Double-Blind Method; Epithelial Sodium Channels; Female; Glomerular Filtration Rate; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Kidney; Male; Middle Aged; Nitric Oxide; Pyrroles; Renal Insufficiency, Chronic; Vascular Stiffness; omega-N-Methylarginine
PubMed: 24697877
DOI: 10.1111/bcp.12390 -
EuroIntervention : Journal of EuroPCR... Apr 2015To investigate in vivo relationships between segmental wall shear stress (WSS), endothelium-dependent vasoreactivity and arterial remodelling.
AIMS
To investigate in vivo relationships between segmental wall shear stress (WSS), endothelium-dependent vasoreactivity and arterial remodelling.
METHODS AND RESULTS
Twenty-four patients with minor angiographic coronary arterial disease (≤30% stenosis severity) underwent intracoronary (IC) salbutamol provocation during intravascular ultrasound (IVUS)-upon-Doppler guidewire imaging. Macrovascular response (change in segmental lumen volume [SLV] at baseline and following IC salbutamol), plaque burden (percent atheroma volume [PAV]), remodelling indices (RI), eccentricity indices (EI) and WSS were evaluated in 179 consecutive 5 mm coronary segments. Baseline WSS was directly related to endothelium-dependent epicardial coronary vasomotion (% change SLV, coefficient 17.2, p=0.004), and inversely related to RI (coefficient -0.23, p=0.02) and EI (coefficient -10.0, p=0.001). Baseline WSS was lower in segments displaying endothelial dysfunction (defined as any change in SLV ≤0) compared with preserved function (0.66±0.33 vs. 0.71±0.22 N/m2, p=0.046). Independent of plaque burden, segments with the lowest tertile of WSS displayed less vasodilatation, or vasoconstriction, than segments with the highest tertile of WSS. Higher plaque burden segments harbouring the lowest tertiles of WSS displayed vasoconstriction, expansive arterial remodelling and greater plaque eccentricity.
CONCLUSIONS
In patients with stable coronary syndromes and minor angiographic coronary disease, coronary segments with lower in vivo WSS values display functional and morphological features of plaque vulnerability.
Topics: Adrenergic beta-2 Receptor Agonists; Albuterol; Coronary Angiography; Coronary Artery Disease; Coronary Stenosis; Coronary Vessels; Endothelium, Vascular; Enzyme Inhibitors; Female; Humans; Male; Middle Aged; Severity of Illness Index; Shear Strength; Ultrasonography, Doppler; Ultrasonography, Interventional; Vascular Remodeling; Vasodilation; omega-N-Methylarginine
PubMed: 24425248
DOI: 10.4244/EIJV10I12A249