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Docosahexaenoic acid reduces resting blood pressure but increases muscle sympathetic outflow compared with eicosapentaenoic acid in healthy men and women.
Lee, JB, Notay, K, Klingel, SL, Chabowski, A, Mutch, DM, Millar, PJ
American journal of physiology. Heart and circulatory physiology. 2019;(4):H873-H881
Abstract
Supplementation with monounsaturated or ω-3 polyunsaturated fatty acids ( n-3 PUFA) can lower resting blood pressure (BP) and reduce the risk of cardiovascular events. The independent contributions of the n-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on BP, and the mechanisms responsible, are unclear. We tested whether EPA, DHA, and olive oil (OO), a source of monounsaturated fat, differentially affect resting hemodynamics and muscle sympathetic nerve activity (MSNA). Eighty-six healthy young men and women were recruited to participate in a 12-wk, randomized, double-blind trial examining the effects of orally supplementing ~3 g/day of EPA ( n = 28), DHA ( n = 28), or OO ( n = 30) on resting hemodynamics; MSNA was examined in a subset of participants ( n = 31). Both EPA and DHA supplements increased the ω-3 index ( P < 0.01). Reductions in systolic BP were greater [adjusted intergroup mean difference (95% confidence interval)] after DHA [-3.4 mmHg (-0.9, -5.9), P = 0.008] and OO [-3.0 mmHg (-0.5, -5.4), P = 0.01] compared with EPA, with no difference between DHA and OO ( P = 0.74). Reductions in diastolic BP were greater following DHA [-3.4 mmHg (-1.3,-5.6), P = 0.002] and OO [-2.2 mmHg (0.08,-4.3), P = 0.04] compared with EPA. EPA increased heart rate compared with DHA [4.2 beats/min (-0.009, 8.4), P = 0.05] and OO [4.2 beats/min, (0.08, 8.3), P = 0.04]. MSNA burst frequency was higher after DHA [4 bursts/min (0.5, 8.3), P = 0.02] but not OO [-3 bursts/min (-6, 0.6), P = 0.2] compared with EPA. Overall, DHA and OO evoked similar responses in resting BP; however, DHA, but not OO, increased peripheral vasoconstrictor outflow. These findings may have implications for fatty acid supplementation in clinical populations characterized by chronic high BP and sympathetic overactivation. NEW & NOTEWORTHY We studied the effects of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and olive oil supplementation on blood pressure (BP) and muscle sympathetic nerve activity (MSNA). After 12 wk of 3 g/day supplementation, DHA and olive oil were associated with lower resting systolic and diastolic BPs than EPA. However, DHA increased MSNA compared with EPA. The reductions in BP with DHA likely occur via a vascular mechanism and evoke a baroreflex-mediated increase in sympathetic activity.
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Need for prophylactic application of verapamil in transradial coronary procedures: a randomized trial. The VITRIOL (is Verapamil In TransRadial Interventions OmittabLe?) trial.
Hizoh, I, Majoros, Z, Major, L, Gulyas, Z, Szabo, G, Kerecsen, G, Korda, A, Molnar, F, Kiss, RG
Journal of the American Heart Association. 2014;(2):e000588
Abstract
BACKGROUND Verapamil is traditionally applied prophylactically in transradial procedures to prevent radial artery spasm. However, verapamil may have side effects and is contraindicated in some clinical settings. METHODS AND RESULTS During an investigator-initiated, randomized, double-blind trial, we evaluated the need for preventive verapamil administration. After vascular access was established, patients received either 5 mg verapamil (n=297) or placebo (n=294). We compared the rate of access site conversions as primary end point using a superiority margin of 5%. Occurrence of code breaks (composite of conversions and unplanned use of verapamil), overall verapamil use, procedural and fluoroscopic times, contrast volume, and subjective pain were investigated as secondary end points. The rate of access site conversions was not different in the 2 arms (placebo 1.7% versus verapamil 0.7%, P=0.28, difference 1.0%, 95% CI for the difference -1.1% to 3.3%). Proportion of code breaks was similar in the 2 groups (3.4% versus 1.3%, P=0.11), whereas overall verapamil use was markedly lower in the placebo arm (2.0% versus 100%, P<0.0001). Procedural time (median [IQR] 16.0 minutes [9.0 to 30.0 minutes] versus 17.0 minutes [10.0 to 31.0 minutes], P=0.37), fluoroscopic time (4.4 minutes [2.1 to 9.6 minutes] versus 4.8 minutes [2.4 to 10.7 minutes], P=0.28), contrast volume (72.5 mL [48.0 to 146.0 mL] versus 75.5 mL [47.0 to 156.5 mL], P=0.74), and pain score (P for trend=0.12) were comparable in the 2 groups. CONCLUSIONS The preventive use of verapamil may be unnecessary for transradial procedures. The omission of prophylactic verapamil may not only reduce the rate of potential complications related to the drug but also allow the safe extension of the transradial method to those with contraindications to verapamil. CLINICAL TRIAL REGISTRATION URL http://www.clinicaltrials.gov. Unique identifier: NCT01402427.
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Effect of vitamin C on hyperoxia-induced vasoconstriction in exercising skeletal muscle.
Ranadive, SM, Joyner, MJ, Walker, BG, Taylor, JL, Casey, DP
Journal of applied physiology (Bethesda, Md. : 1985). 2014;(10):1207-11
Abstract
Hyperoxia can cause substantial reductions in peripheral and coronary blood flow at rest and during exercise, which may be caused by reactive oxygen species (ROS) generated during hyperoxia. The aim of this study was to investigate the role of ROS in hyperoxia-induced reductions in skeletal muscle blood flow during forearm exercise. We hypothesized that infusion of vitamin C would abolish the effects of hyperoxia on the forearm blood flow (FBF) responses to exercise. Twelve young healthy adults performed rhythmic forearm handgrip exercise (10% of maximum voluntary contraction for 5 min) during normoxia and hyperoxia. For each condition, two trials were conducted with intra-arterial administration of saline or vitamin C. FBF was measured using Doppler ultrasound. During hyperoxia with saline, FBF and forearm vascular conductance (FVC) were 86.3 ± 5.1 and 86.8 ± 5.2%, respectively, of the normoxic values (100%) (P < 0.05). During vitamin C, hyperoxic FBF and FVC responses were 90.9 ± 4.2 and 90.9 ± 4.1%, respectively, of the normoxic values (P = 0.57 and 0.59). Subjects were then divided into three subgroups based on their percent decrease in FBF (>20, 10-20, and <10%) during hyperoxia. In the subgroup that demonstrated the greatest hyperoxia-induced changes (>20%), FBF and FVC during hyperoxia were 67.1 ± 4.0 and 66.8 ± 3.6%, respectively, of the normoxic values. Vitamin C abolished these effects on FBF and FVC with values that were 102.0 ± 5.2 and 100.8 ± 6.1%, respectively. However, vitamin C had no effect in the other two subgroups. This analysis is consistent with the idea that ROS generation blunts the FBF responses to exercise in the subjects most affected by hyperoxia.
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A randomised controlled trial of induced hypermagnesaemia following aneurysmal subarachnoid haemorrhage.
Bradford, CM, Finfer, S, O'Connor, A, Yarad, E, Firth, R, McCallister, R, Harrington, T, Steinfort, B, Faulder, K, Assaad, N, et al
Critical care and resuscitation : journal of the Australasian Academy of Critical Care Medicine. 2013;(2):119-25
Abstract
BACKGROUND The effect of serum magnesium concentration on the incidence of cerebral arterial vasospasm following aneurysmal subarachnoid haemorrhage (SAH) is unclear. OBJECTIVE To test whether induced hypermagnesaemia reduces the incidence of cerebral arterial vasospasm following aneurysmal SAH. METHODS The study was conducted at two tertiary hospitals in Australia and patients were recruited between 1 April 2005 and 31 December 2009. Within 72 hours of aneurysmal SAH, patients were randomly assigned to a high or normal target for serum magnesium concentration (1.60-2.50 mmol/L or 0.65-1.05 mmol/L, respectively). The primary end point was cerebral arterial vasospasm diagnosed by blinded assessment of digital subtraction angiography. Secondary outcomes included severity of vasospasm and functional recovery at 90 days. Analysis was by intention to treat. RESULTS Of 162 patients, 81 were assigned to the normal range group and 81 were assigned to the high-range group; the primary outcome was available for 78 and 79 patients, respectively. The groups had similar baseline characteristics. Vasospasm occurred in 40 patients (50.6%) and 50 patients (64.1%) assigned to high-range and normal-range groups, respectively (adjusted OR, 0.51; 95% CI, 0.26-1.02; P = 0.06). At 90 days, neurological recovery between the groups was not significantly different (adjusted OR for worse outcome, 0.71; 95% CI, 0.39-1.32; P = 0.28). Patients in the high-range group were treated with more noradrenaline to support arterial blood pressure (79 [16- 218] mg) v 59 [14-129] mg; P = 0.03) and had lower mean (SD) serum calcium concentration (1.9 [0.2] mmol/L v 2.1 [0.2] mmol/L, P < 0.001). CONCLUSION Patients assigned a higher serum magnesium concentration had a reduced incidence of vasospasm as seen by angiography, but the difference was not statistically significant. Clinically significant outcomes were not different between groups. A firm recommendation for induced hypermagnesaemia cannot be made from this study. TRIAL REGISTRATION NUMBER ACTRN12605000058673.
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Water ingestion reduces skin blood flow through sympathetic vasoconstriction.
Lu, CC, Li, MH, Lin, TC, Chen, TL, Chen, RM, Tung, CS, Tseng, CJ, Ho, ST
Clinical autonomic research : official journal of the Clinical Autonomic Research Society. 2012;(2):63-9
Abstract
OBJECTIVE Water ingestion induces a pressor effect in patients with efferent baroreflex impairment and a mild pressor effect in elderly healthy subjects. However, water raised the total peripheral vascular resistance (TPR) without a prominent change in blood pressure in young healthy subjects. We try to investigate whether water elicits a cardiovascular response via regulating regional skin blood flow (SkBF) in young healthy subjects. METHODS In a randomized, controlled, crossover fashion, 15 healthy male subjects (19-27 years old) ingested either 500 (water session) or 50 ml of water (control). The heart rate, blood pressure, cardiac index, and TPR were measured using a Task Force Monitor. A laser Doppler velocimeter was used to determine the change in the SkBF at the left thenar eminence. Plasma catecholamines and their metabolites were also measured. RESULTS At 25 min after ingestion of 500 ml water, the cardiac index and SkBF significantly decreased compared to control. In contrast, the TPR significantly increased after ingestion of 500 ml water. Plasma dihydroxyphenylalanine significantly increased at 25 min after water. INTERPRETATION Water ingestion decreases the cardiac index to compensate for the increase in the TPR, leading to no net change in blood pressure in young healthy subjects. This study suggests that water decreases the SkBF, a mechanism that might account partly for the nature of osmopressor response to water in young healthy subjects.
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Oral vitamin C enhances the adrenergic vasoconstrictor response to local cooling in human skin.
Yamazaki, F
Journal of applied physiology (Bethesda, Md. : 1985). 2012;(10):1689-97
Abstract
Local administration of ascorbic acid (Asc) at a supraphysiological concentration inhibits the cutaneous vasoconstrictor response to local cooling (LC). However, whether orally ingesting Asc inhibits the LC-induced vasoconstrictor response remains unknown. The purpose of the present study was to examine the acute influence of oral Asc on the adrenergic vasoconstrictor response to LC in human skin. In experiment 1, skin blood flow (SkBF) was measured by laser-Doppler flowmetry at three sites (forearm, calf, palm). The three skin sites were locally cooled from 34 to 24°C at -1°C/min and maintained at 24°C for 20 min before (Pre) and 1.5 h after (Post) oral Asc (2-g single dose) or placebo supplementation. Cutaneous vascular conductance (CVC) was calculated as the ratio of SkBF to blood pressure and expressed relative to the baseline value before LC. Oral Asc enhanced (P < 0.05) the reductions in CVC in the forearm (Pre, -50.3 ± 3.3%; Post, -57.8 ± 2.2%), calf (Pre, -52.6 ± 3.7%; Post, -66.1 ± 4.3%), and palm (Pre, -46.2 ± 6.2%; Post, -60.4 ± 5.6%) during LC. The placebo did not change the responses at any site. In experiment 2, to examine whether the increased vasoconstrictor response caused by oral Asc is due to the adrenergic system, the release of neurotransmitters from adrenergic nerves in forearm skin was blocked locally by iontophoresis of bretylium tosylate (BT). Oral Asc enhanced (P < 0.05) the reductions in CVC at untreated control sites but did not change the responses at BT-treated sites during LC. In experiment 3, to further examine whether adrenergically mediated vasoconstriction is enhanced by oral Asc, 0.1 mM tyramine was administered using intradermal microdialysis in the forearm skin at 34°C in the Pre and Post periods. Oral Asc increased (P < 0.05) the tyramine-induced reduction in CVC. These findings suggest that oral Asc acutely enhances the cutaneous vasoconstrictor responses to LC through the modification of adrenergic sympathetic mechanisms.
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Ketorolac alters blood flow during normothermia but not during hyperthermia in middle-aged human skin.
Holowatz, LA, Jennings, JD, Lang, JA, Kenney, WL
Journal of applied physiology (Bethesda, Md. : 1985). 2009;(4):1121-7
Abstract
In young healthy humans full expression of reflex cutaneous vasodilation is dependent on cyclooxygenase (COX)- and nitric oxide synthase (NOS)-dependent mechanisms. Chronic low-dose aspirin therapy attenuates reflex cutaneous vasodilation potentially through both platelet and vascular COX-dependent mechanisms. We hypothesized the contribution of COX-dependent vasodilators to reflex cutaneous vasodilation during localized acute COX inhibition would be attenuated in healthy middle-aged humans due to a shift toward COX-dependent vasoconstrictors. Four microdialysis fibers were placed in forearm skin of 13 middle-aged (53 +/- 2 yr) normotensive healthy humans, serving as control (Ringer), COX-inhibited (10 mM ketorolac), NOS-inhibited (10 mM N(G)-nitro-l-arginine methyl ester), and combined NOS- and COX-inhibited sites. Red blood cell flux was measured over each site by laser-Doppler flowmetry as reflex vasodilation was induced by increasing oral temperature (T(or)) 1.0 degrees C using a water-perfused suit. Cutaneous vascular conductance was calculated (CVC = flux/mean arterial pressure) and normalized to maximal CVC (CVC(max); 28 mM sodium nitroprusside). CVC(max) was not affected by localized microdialysis drug treatment (P > 0.05). Localized COX inhibition increased baseline (18 +/- 3%CVC(max); P < 0.001) compared with control (9 +/- 1%CVC(max)), NOS-inhibited (7 +/- 1%CVC(max)), and combined sites (10 +/- 1%CVC(max)). %CVC(max) in the COX-inhibited site remained greater than the control site with DeltaT(or) < or = 0.3 degrees C; however, there was no difference between these sites with DeltaT(or) > or = 0.4 degrees C. NOS inhibition and combined COX and NOS inhibition attenuated reflex vasodilation compared with control (P < 0.001), but there was no difference between these sites. Localized COX inhibition with ketorolac significantly augments baseline CVC but does not alter the subsequent skin blood flow response to hyperthermia, suggesting a limited role for COX-derived vasodilator prostanoids in reflex cutaneous vasodilation and a shift toward COX-derived vasoconstrictors in middle-aged human skin.
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Chronic treatment with long-acting nifedipine reduces vasoconstriction to endothelin-1 in essential hypertension.
Sudano, I, Virdis, A, Taddei, S, Spieker, L, Corti, R, Noll, G, Salvetti, A, Luscher, TF
Hypertension (Dallas, Tex. : 1979). 2007;(2):285-90
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Abstract
Essential hypertension is associated with enhanced biological activity of endothelin-1 (ET-1) and impaired endothelium-dependent vasodilatation. Dihydropyridine calcium antagonists have antioxidant activity in vitro, and they improve endothelial function in vivo. We tested whether calcium antagonists also influence the biological activity of ET-1 in essential hypertensive (EH) patients in the presence and absence of hypercholesterolemia. In 9 healthy subjects (normotensive [NT] subjects, age: 48.3+/-7.6 years; blood pressure: 118+/-8.6/69+/-5.4 mm Hg) and 21 EH subjects (age: 50.0+/-7.8 years; blood pressure: 164.4+/-5.4/103.8+/-4.4 mm Hg), we studied forearm blood flow and its modification induced by intrabrachial administration of ET-1, phenylephrine, acetylcholine, and sodium nitroprusside at baseline and after 24 weeks of treatment with a nifedipine gastrointestinal therapeutic system (30 to 60 mg per day). At baseline, the first dose of ET-1 (0.5 microg/100 mL of forearm tissue per minute) caused a slight vasodilatation in NT but not in EH subjects, whereas the following higher doses caused a comparable dose-dependent vasoconstriction in EH and NT subjects. The effect of acetylcholine was significantly reduced in EH as compared with NT subjects. In contrast, sodium nitroprusside and phenylephrine had similar effects in NT and EH subjects. After chronic treatment with the nifedipine gastrointestinal therapeutic system, the vasoconstrictor effect induced by both ET-1 and phenylephrine was significantly blunted, whereas the response to acetylcholine was significantly increased and the vasodilation to sodium nitroprusside unchanged. Hypercholesterolemic EH subjects showed a further reduced response to acetylcholine compared with normocholesterolemic EH subjects, and the nifedipine gastrointestinal therapeutic system restored the vasodilation to acetylcholine in this subgroup. In conclusion, in EH subjects, chronic treatment with a long-acting dihydropyridine calcium antagonist not only exhibits a blood pressure-lowering effect but also reduces ET-1-induced vasoconstriction and improves endothelium-dependent vasodilation. Those vasculoprotective effects may importantly contribute to a reduction in major clinical events seen during treatment with these compounds.
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Systemic sensitivity to corticosteroids in smokers with asthma.
Livingston, E, Chaudhuri, R, McMahon, AD, Fraser, I, McSharry, CP, Thomson, NC
The European respiratory journal. 2007;(1):64-71
Abstract
Cigarette smokers with asthma are insensitive to the therapeutic effects of corticosteroids. It is not known whether this insensitivity to corticosteroids in smokers affects tissue sites beyond the airways. A total of 75 asthmatic subjects (39 smokers) and 78 healthy controls (30 smokers) were recruited to an observational study. The cutaneous and peripheral blood lymphocyte responses to corticosteroids were measured. The cutaneous vasoconstrictor response to topical beclometasone was measured by applying different concentrations of beclometasone solutions to the skin in a random double-blind manner. The degree of blanching at each concentration was graded after 18 h. The sensitivity of peripheral blood lymphocytes to corticosteroids was assessed by measuring the suppressive effect of dexamethasone on lymphocyte proliferation stimulated by phytohaemagglutinin (PHA). Total mean+/-sd cutaneous vasoconstrictor response score to beclometasone was reduced in smokers with asthma to 5.39+/-3.58 versus 7.26+/-3.05 in never-smokers with asthma; and in all smokers to 6.47+/-3.33 versus 7.86+/-2.81 in all never-smokers. The sensitivity to corticosteroids of lymphocytes stimulated by PHA was similar between groups. In conclusion, smokers with asthma have an impaired cutaneous vasoconstrictor response to topical corticosteroids compared with never-smokers with asthma. This finding suggests that the insensitivity to corticosteroids in smokers with asthma affects tissue sites other than the airways.
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Postprandial effect of n-3 polyunsaturated fatty acids on apolipoprotein B-containing lipoproteins and vascular reactivity in type 2 diabetes.
Hilpert, KF, West, SG, Kris-Etherton, PM, Hecker, KD, Simpson, NM, Alaupovic, P
The American journal of clinical nutrition. 2007;(2):369-76
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Abstract
BACKGROUND Plasma lipoproteins may be classified by their apolipoprotein composition. The lipoprotein subclass containing apolipoproteins B and C (LpB:C) is considered the most atherogenic. OBJECTIVE We evaluated the acute effects of individual fatty acids on apolipoprotein B (apo B)-containing lipoproteins in adults with type 2 diabetes (n = 15). DESIGN We administered 3 meals in a randomized, double-blind, crossover design. Treatments contained skim milk and 50 g fat from high-oleic acid safflower and canola oils (monounsaturated fatty acid; MUFA), MUFA + 3.5 g alpha-linolenic acid (ALA; MUFA + ALA) from high-ALA canola oil, or MUFA + 4.0 g both eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA; MUFA + EPA/DHA) from sardine oil. Apo B, LpB, LpB:C, LpB:E + LpB:C:E, and LpA-II:B:C:D:E were measured at baseline and 2 and 4 h after the meal. Flow-mediated dilation was measured at baseline and 4 h after the meal. RESULTS The treatments significantly increased apo B and LpB postprandially (P < 0.03 for both), but the magnitude of the changes did not differ significantly between the treatments. The postprandial change in LpB:C was 23% lower after MUFA + EPA/DHA than after MUFA (treatment x time interaction, P < 0.0001). MUFA + ALA attenuated the increase in LpA-II:B:C:D:E in those with high triacylglycerols (≥1.69 mmol/L) but was the only treatment to significantly increase this particle in those with low triacylglycerols (treatment x group interaction, P < 0.0001). Examination of change scores did not reveal the source of the interaction of treatment and time (P < 0.007) for LpB:E + LpB:C:E. Furthermore, the subjects with the largest increases in LpB:C exhibited the largest impairment in endothelial function. CONCLUSIONS The results suggest that unsaturated fatty acids differentially affect concentrations of apo B-containing lipoprotein subclasses. A rise in LpB:C adversely affects endothelial function. Meals containing MUFA + EPA/DHA attenuated the postprandial rise in LpB:C and the impairment of endothelial function.