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Results for “flow mediated dilatation”

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At least 19 recordsLinked to original sources

PubMed1992

Potassium channel openers dilate large epicardial coronary arteries in conscious dogs by an indirect, endothelium-dependent mechanism.

Cromakalim and pinacidil, two potassium channel openers, dilate both large and small coronary arteries in conscious dogs. Because flow-mediated dilation of large arteries is endothelium-dependent, the consequences of in vivo endothelium removal (balloon denudation) on the response of large epicardial coronary arteries to cromakalim (10 micrograms/kg) and pinacidil (30 micrograms/kg) were investigated in six dogs chronically instrumented for the measurement of arterial pressure, left circumflex coronary artery diameter and coronary blood flow. Endothelium removal abolished the dilation of large coronary arteries induced by acetylcholine (endothelium-dependent dilation) and reactive hyperemia (flow-mediated dilation), but only slightly reduced (-18%) that induced by nitroglycerin. Before endothelium removal, both cromakalim and pinacidil induced a significant decrease in coronary resistance (-71 +/- 2 and -63 +/- 2%, respectively) and a significant increase in coronary diameter (8.5 +/- 1.3 and 6.7 +/- 0.9%). After endothelium removal, the decreases in coronary resistance were unaffected, but the increases in coronary diameter were reduced by 93 and 98% as compared to predenudation responses with cromakalim and pinacidil, respectively (both P < .01). In contrast, in vitro studies performed in isolated large epicardial coronary arteries obtained from five additional dogs showed that cromakalim evoked relaxations that were not affected by prior in vivo endothelium removal. Thus, despite the presence of potassium channels in isolated denuded large coronary arteries, our data demonstrate that cromakalim- and pinacidil-induced dilation of large arteries in vivo is an indirect, flow-mediated effect which is entirely endothelium-dependent.

Acetylcholine↗

PubMed1992

Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis.

Endothelial dysfunction is an early event in experimental studies of atherogenesis, preceding formation of plaques. We have devised a non-invasive method for testing endothelial function, to find out whether abnormalities are present in symptom-free children and young adults at high risk of atherosclerosis. With high-resolution ultrasound, we measured the diameter of the superficial femoral and brachial arteries at rest, during reactive hyperaemia (with increased flow causing endothelium-dependent dilatation), and after sublingual glyceryl trinitrate (GTN; causing endothelium-independent dilatation) in 100 subjects--50 controls without vascular risk factors (aged 8-57 years), 20 cigarette smokers (aged 17-62 years), 10 children with familial hypercholesterolaemia (FH; aged 8-16 years), and 20 patients with established coronary artery disease (CAD). Adequate scans were obtained in all but 6 cases. Flow-mediated dilatation was observed in arteries from all control subjects. Dilatation was inversely related to baseline vessel diameter (r = -0.81, p < 0.0001); in arteries of 6.0 mm or less, mean dilatation was 10 (SE 2)%. In smokers, FH children, and adults with CAD, flow-mediated dilatation was much reduced or absent (p < 0.001 for comparison with each relevant control group). Dilatation in response to GTN was present in all groups. Endothelial dysfunction is present in children and adults with risk factors for atherosclerosis, such as smoking and hypercholesterolaemia, before anatomical evidence of plaque formation in the arteries studied. This may be an important early event in atherogenesis.

Adolescent↗

PubMed2026

The Association Between NT-Pro BNP, Nephropathy and Endothelial Dysfunction in Patients With Type 2 Diabetes Mellitus.

BACKGROUND: N-terminal pro-B-type natriuretic peptide (NT-Pro BNP) is an established biomarker of heart failure and has been recommended for cardiovascular risk stratification in type 2 diabetes mellitus (T2DM). However, its relationship with diabetic nephropathy and endothelial dysfunction across varying stages of kidney impairment remains unclear. This study examined the associations of NT-Pro BNP, renal impairment, albuminuria and endothelial dysfunction in patients with T2DM without overt heart failure. METHODS: A comparative cross-sectional study was conducted among 192 adults with T2DM. Participants were stratified by KDIGO eGFR groups (≥ 90, 60-89, 30-59 mL/min/1.73m2). NT-Pro BNP was considered abnormal at a cut-off of ≥ 125 pg/mL. Albuminuria was categorized using the urinary albumin-to-creatinine ratio (uACR). Endothelial function was assessed by brachial artery flow-mediated dilatation (FMD). Logistic regression analysis was performed to identify independent factors of elevated NT-Pro BNP, with p-values < 0.05 considered statistically significant. RESULTS: NT-Pro BNP levels were significantly higher in the lower eGFR groups compared with normal eGFR (204.3 vs. 96.8 vs. 62.2 pg/mL, p < 0001). A weak but significant positive correlation was observed between NT-Pro BNP and uACR (r = 0.31, p < 0.001). However, no significant association was found between NT-Pro BNP and FMD (p = 0.388). Following multivariable adjustments, older age (adjusted OR 1.14, 95% CI: 1.06-1.23, p < 0.001), higher systolic blood pressure (adjusted OR 1.05, 95% CI: 1.02-1.08, p = 0.010), lower eGFR (adjusted OR 0.97, 95% CI: 0.95-0.99, p = 0.003) and beta-blocker use (adjusted OR 4.65, 95% CI: 1.61-13.45, p < 0.001) were independently associated with elevated NT-Pro BNP. CONCLUSION: In patients with T2DM without overt heart failure, elevated NT-Pro BNP showed a statistically significant association with lower eGFR and higher albuminuria. Moderate to severe albuminuria becomes an independent factor for elevated NT-Pro BNP after adjustment excluding eGFR. The lack of association with endothelial dysfunction suggests that NT-Pro BNP may reflect different pathophysiological pathways. NT-Pro BNP may serve as a useful biomarker for early cardiovascular risk stratification and identification of individuals at risk of pre-heart failure in diabetic kidney disease.

NT‐Pro BNP↗

PubMed2026

Endothelial-mitochondrial coupling in mitochondrial disease: A systematic review and quantitative synthesis of vascular, biochemical, and oxidative bioenergetic dysfunction.

INTRODUCTION: Mitochondrial diseases are multisystem disorders in which defects in oxidative phosphorylation disrupt cellular bioenergetics and redox signaling across the vasculature and heart. Because mitochondrial function is closely linked to endothelial nitric oxide (NO) production, we hypothesized that mitochondrial diseases manifest as a NO-deficiency endotheliopathy affecting conduit and microvascular function. To evaluate this, we performed a systematic review with quantitative synthesis of human studies reporting vascular reactivity, biochemical NO production, or myocardial metabolic imaging, aiming to define the magnitude of impairment and responsiveness to NO-precursor therapy (l-arginine or l-citrulline). METHODS: Following PRISMA 2020 guidelines, we conducted a comprehensive search (inception-October 2025) identifying clinical studies of genetically or clinically confirmed mitochondrial disease with quantitative endothelial or bioenergetic endpoints. Eligible measures included flow-mediated dilation (FMD), reactive hyperemia index (RHI), passive-leg-movement (PLM) hyperemia, absolute synthesis rate of NO metabolites (ASR NOm), and positron emission tomography (PET)-derived myocardial oxidative indices (k mono , DP/k mono ). Quantitative synthesis used Hedges g for between-group comparisons and standardized mean change (SMC) for within-subject responses. Risk of bias was evaluated using ROBINS-I and a modified Newcastle-Ottawa Scale. RESULTS: Seven studies met these inclusion criteria, comprising 76 mitochondrial-disease subjects and 81 controls (ages 8-63 years). Across all vascular and metabolic domains, mitochondrial disease was associated with marked endothelial and bioenergetic impairment. Macro- and microvascular dysfunction, reflected by reduced FMD, RHI, and PLM hyperemia, demonstrated severe endothelium-specific abnormalities. Biochemical assays showed diminished NO synthesis. Myocardial PET imaging revealed reduced oxidative rate constants and increased energetic inefficiency despite preserved perfusion. Nitric oxide synthesis-precursor therapy was associated with improved endothelial reactivity (increased FMD, RHI, and ASR NOm) and significant, modest improvements in myocardial oxidative metabolism, consistent with partial restoration of endothelial NO signaling. Effect sizes collectively supported a reversible NO-deficiency endotheliopathy. The risk-of-bias assessment indicated moderate-to-good methodological quality, with limitations primarily related to small sample sizes and nonrandomized designs. CONCLUSIONS: Mitochondrial disease is characterized by significant impairments in vascular reactivity, NO signaling, and myocardial bioenergetics. Improvements in endothelial function and NO synthesis following l-arginine or l-citrulline supplementation are consistent with a role for impaired endothelial NO signaling in the vascular manifestations of mitochondrial disease. These findings highlight the vascular endothelium as a potential therapeutic target and underscore the need for future clinical intervention trials that use standardized vascular and bioenergetic endpoints.

and stroke-like episodes (MELAS)↗

PubMed2026

Targeted Nrf2 activation improves vascular endothelial function with aging and prevents vascular dysfunction following disuse in younger and older adults.

Aging and physical inactivity/disuse contribute to cardiovascular disease, which is attributable, in part, to vascular endothelial dysfunction associated with impaired nuclear-factor erythroid 2-related factor 2 (Nrf2) signaling. However, the ability to augment Nrf2 activation and its effects on age- and disuse-related vascular dysfunction in humans remains limited. In a double-blind, randomized, placebo-controlled study design 20 younger adults (8M/12F, age 27 ± 7 y) and 24 older adults (12M/12F, age 67 ± 8 y) were randomized to receive either placebo or PB125 (200 mg/day, Nrf2 activator) across three visits: baseline, 2 weeks of supplementation, and following either 5 days of bed rest (old) or 2 weeks of limb immobilization (young). Brachial and popliteal artery flow-mediated dilation (FMD), passive leg movement-induced (PLM) leg blood flow (LBF) and vascular conductance (LVC) and serum antioxidant status (superoxide dismutase, SOD) were assessed at each timepoint. Compared to placebo, 2 weeks of PB125 increased brachial (PB125: 2.8 ± 1.5 to 3.8 ± 1.3%, p < 0.0001) and popliteal FMD (PB125: 1.5 ± 1.5 to 2.3 ± 1.4%, p = 0.033) in older, but not younger adults (both, p > 0.27). During bed rest, PB125 preserved brachial (3.8 ± 1.3 to 3.6 ± 1.4%, p = 0.543) and popliteal FMD (2.3 ± 1.4 to 2.7 ± 1.4%, p = 0.269), LVC (1.1 ± 0.8 to 1.1 ± 1.5 AUC, p = 0.530) and circulating SOD concentrations (28.3 ± 7.2 to 28.6 ± 8.6 U/mL, p = 0.888) in older adults compared to placebo (all, p < 0.05). Following limb immobilization, PB125 preserved popliteal FMD (4.4 ± 2.8 to 3.4 ± 1.8%, p = 0.302) in younger adults compared to placebo (p < 0.05). These findings demonstrate targeted Nrf2 activation with PB125 improves age-related vascular endothelial dysfunction while preserving vascular function and antioxidant capacity following periods of disuse.

Humans↗

PubMed2026

Orange juice and hesperidin increase flavanone exposure without detectable short-term vascular benefits: a randomized crossover trial.

Orange juice is a major dietary source of hesperidin, a citrus flavanone with vascular protective effects in experimental models. However, whether nutritionally realistic intake levels induce measurable benefits in humans remains unclear. We investigated the effects of orange juice and hesperidin supplementation, at realistic dietary doses, on vascular function, flavanone bioavailability, and molecular responses. Thirty-seven centrally overweight men completed a randomized, double-blind, controlled, three-period crossover trial with three 6-week interventions separated by washout periods. Participants consumed daily 330 mL of 100% orange juice (OJ), an isoenergetic control beverage (CON), or a hesperidin-enriched control beverage (HESP, 210 mg day-1). Fasting vascular, metabolic and anthropometric parameters were assessed before and after each intervention, with flow-mediated dilation (FMD) as the primary endpoint. Postprandial FMD, circulating flavanone metabolites and oxylipin profiles were evaluated following a standardized high-fat meal challenge, and flavanone bioavailability was assessed by 24 h urinary excretion. Whole-blood transcriptomics were performed in a subset (n = 9). Plasma exposure to phase II hesperetin metabolites (AUC0-6 h) and 24 h urinary excretion were comparable after OJ and HESP, indicating effective hesperidin delivery and limited matrix effects on bioavailability. Neither intervention significantly affected fasting or postprandial FMD, vascular, metabolic or anthropometric parameters, or oxylipin profiles versus CON. Marked interindividual variability was observed in vascular responses and flavanone bioavailability, although treatment effects were unrelated to baseline endothelial function or flavanone exposure. Exploratory transcriptomic analyses suggested modulation of pathways involved in vascular biology following OJ and HESP. Under nutritionally realistic conditions, orange juice and hesperidin induced measurable biological engagement without detectable short-term vascular benefits, highlighting the complexity of linking flavanone exposure to functional vascular outcomes in humans.

Humans↗

PubMed2026

Optimizing physical activity bouts to interrupt sedentary behaviour for cardiometabolic health: a systematic review and meta-analyses of randomized controlled trials.

AIMS: Chronic diseases such as type 2 diabetes mellitus and cardiovascular diseases are leading causes of mortality worldwide, with sedentary behaviour (SB) and physical inactivity recognized as major interrelated risk factors. Prolonged SB, particularly when combined with insufficient physical activity, adversely affects cardiometabolic health. This systematic review aimed to evaluate which characteristics of physical activity (PA) bouts, in terms of frequency, duration, and intensity, are associated with improvements in cardiometabolic outcomes. METHODS AND RESULTS: Studies assessing physical activity interventions compared with sedentary control conditions were included. Eligible studies involved adults aged 18-65 years, with or without cardiometabolic conditions. PubMed, Cochrane Central, Embase, and Web of Science were searched to February 2025. Random-effects models were used to calculate pooled standardized mean differences (SMD) with 95% confidence interval (CI). Subgroup and meta-regression analyses explored potential moderators. A total of 144 studies (247 intervention arms; 2216 participants) were included. Frequent PA bouts reduced blood glucose [SMD -0.22 (95% CI -0.27 to -0.16)]. Longer and/or more intense PA bouts decreased triglycerides [SMD -0.27 (-0.34 to -0.19)], with significant duration × intensity interactions for glucose (P = 0.032) and triglycerides (P < 0.001). Moderate-to-vigorous PA bouts improved endothelial function [flow-mediated dilation SMD 0.88 (0.47-2.24); shear rate SMD 0.54 (0.31-0.78)]. PA bouts also lowered insulin [SMD -0.26 (-0.32 to -0.19)], systolic BP [SMD -0.29 (-0.39 to -0.19)], and diastolic BP [SMD -0.16 (-0.26 to -0.05)]. CONCLUSION: In acute experimental settings, glucose regulation appears to benefit more from frequent PA bouts, while triglyceride responses are more closely related to greater duration and/or intensity. Blood pressure shows favourable acute responses across PA types, whereas higher PA intensity is associated with improved endothelial function. Tailoring strategies to interrupt SB with PA bouts may help inform approaches to improve cardiometabolic health.

Humans↗

PubMed1992

Effect of diabetes mellitus on flow-mediated and endothelium-dependent dilatation of the rat basilar artery.

BACKGROUND AND PURPOSE: Diabetes mellitus may impair endothelium-dependent responses in cerebral arterioles. The basilar artery dilates in response to increases in blood flow. The goal of this study was to examine effects of diabetes mellitus on "flow-mediated" and endothelium-dependent dilatation of the basilar artery. METHODS: Diabetes was induced in rats with 50 mg/kg streptozotocin. Six months later, vessel diameter and velocity of blood flow through the basilar artery were measured using a cranial window in anesthetized rats under baseline conditions and during occlusion of the carotid arteries. Changes in vessel diameter were also measured during topical application of acetylcholine and sodium nitroprusside. RESULTS: With aortic pressure maintained at baseline levels, blood flow velocity through the basilar artery increased similarly in control and diabetic rats during unilateral common carotid artery occlusion and during bilateral occlusion. In control and diabetic rats, diameter of the basilar artery increased by 10 +/- 2% and 10 +/- 4% during unilateral occlusion and by 27 +/- 5% and 31 +/- 4% during bilateral occlusion, respectively. Thus, diabetes did not impair flow-mediated dilatation of the basilar artery. In contrast, dilatation in response to 10(-5) M topical acetylcholine was less in diabetic rats (13 +/- 2%) than in control rats (45 +/- 8%) (p less than 0.05). Dilator responses to nitroprusside were not impaired by diabetes. CONCLUSIONS: The findings suggest that diabetes produces impairment of endothelium-dependent responses to acetylcholine, but not flow-mediated dilatation, in the basilar artery.

Acetylcholine↗

PubMed1992

Nitric oxide does not mediate flow induced endothelium dependent arterial dilatation in the cat.

OBJECTIVE: The aim was to determine whether the endothelium derived nitric oxide formed from L-arginine is the factor which mediates flow induced dilatation of conduit arteries. METHODS: Changes in diameter of feline femoral artery caused by blood flow rate increases, acetylcholine, and ATP were recorded during perfusion with blood in situ before and after the inhibition of endothelium derived nitric oxide synthesis by NG-nitro-L-arginine methyl ester and NG-monomethyl-L-arginine. Fourteen anaesthetised cats of either sex, weight 2.6-3.9 kg, were used for the studies. RESULTS: Intravenous administration of NG-nitro-L-arginine methyl ester and NG-monoethyl-L-arginine in doses 10 and 30 mg.kg-1 evoked a rise in mean systemic arterial pressure, constriction of the femoral artery, and considerable decrease in acetylcholine and ATP induced dilatation. However, it did not affect the dilator response induced by increased blood flow rate. CONCLUSIONS: Flow induced endothelium dependent arterial dilatation is not mediated by nitric oxide or, if nitric oxide is still released in response to flow rate increase, it has a source distinct from L-arginine.

Acetylcholine↗

PubMed1992

[Nitrogen oxide is not an agent of endothelium-mediated arterial dilatation to an increase in the blood flow rate].

I. v. administration of inhibitors of endothelium-mediated synthesis of the oxide of nitrogen raised the arterial blood pressure, constricted the femoral artery and decreased the acetylcholine- and ATP-induced vaso-dilatation in anesthetized cats. However, the dilatation induced by an increased blood flow velocity, was not affected. The data obtained suggest that the endothelium-dependent arterial dilatation is not mediated by oxide of nitrogen formed from L-arginine.

Acetylcholine↗

PubMed1992

Differential effects of nitrovasodilators, K(+)-channel openers, and nicorandil on large and small coronary arteries in conscious dogs.

When administered intravenously to conscious dogs, nicorandil, nitrovasodilators (nitroglycerin and SIN-1), and the K(+)-channel opener cromakalim exhibited marked differential effects on large epicardial and small resistance coronary arteries. Nitrovasodilators markedly increased the left circumflex coronary artery diameter at doses at which coronary resistance was not significantly decreased. In contrast, both cromakalim and nicorandil dilated large and small coronary arteries in the same conditions. When coronary blood flow was held to its control value by partial inflation of a hydraulic occluder implanted around the artery, the nitroglycerin- and nicorandil-induced increases in large coronary diameter remained unchanged whereas the response to cromakalim was reduced significantly. This coronary dynamic profile indicates that both nitrovasodilators and nicorandil directly dilate large coronary vessels, whereas the effect of cromakalim on these vessels is mediated partially through a flow-dependent mechanism. This suggests that nicorandil mainly dilates large coronary arteries through its nitroglycerin-like properties, whereas its ability to dilate coronary resistance vessels depends mainly on its K(+)-channel opener-like properties.

Animals↗

PubMed1992

Effect of local intra-arterial NG-monomethyl-L-arginine in patients with hypertension: the nitric oxide dilator mechanism appears abnormal.

OBJECTIVE: There is indirect evidence that the nitric oxide system may be impaired in hypertensive patients. The objective of this study was to examine basal nitric oxide-mediated dilation in hypertensive patients. DESIGN: The forearm blood flow (FBF) response to noradrenaline and NG-monomethyl-L-arginine (L-NMMA), a stereospecific inhibitor of nitric oxide synthesis, was compared in seven untreated hypertensive patients and 17 normotensive controls. METHODS: Drugs were infused locally into the brachial artery and FBF measured using venous occlusion plethysmography. RESULTS: In normotensives noradrenaline (60, 120 and 240 pmol/min) and L-NMMA (1,2 and 4 mumol/min) produced similar reductions in resting FBF. In the hypertensives L-NMMA was significantly less effective than noradrenaline, such that the threshold dose for L-NMMA vasoconstriction was increased and the overall response to L-NMMA reduced. Furthermore, when noradrenaline was used as an internal control there was a significant negative relationship between the response to L-NMMA and blood pressure. When the responses to L-NMMA and noradrenaline were compared between groups, the response to L-NMMA was significantly less in hypertensives compared with normotensives, whereas there was no statistical difference in the response to noradrenaline between the two groups. CONCLUSIONS: The results suggest an abnormality of basal nitric oxide-mediated dilation in the forearm arteriolar bed of patients with untreated essential hypertension.

Adult↗

PubMed1992

Adrenergic vasomotor responses in nasal mucosa of hooded seals.

In seals respiratory heat and water losses are restricted through nasal heat exchange. The heat exchange efficiency is apparently controlled through adjustments in the nasal mucosal blood flow rate and/or pattern. In this study the adrenergic mechanisms involved in regulation of mucosal blood flow were investigated. The nasal mucosal vasculature of 14 newly killed hooded seal (Cystophora cristata) pups was perfused by a constant-flow peristaltic pump with 37 degrees C oxygenated modified Krebs solution via the sphenopalatine arteries. The effects of single-dose injections of various drugs on resistance to flow were monitored with a pressure transducer. Epinephrine, norepinephrine, alpha 1-adrenoceptor agonist phenylephrine, alpha 2-agonist clonidine, beta 1-agonist dobutamine, and beta 2-agonist terbutaline caused transient pressure increases that were blocked by alpha-adrenoceptor antagonists. Papaverine and vasoactive intestinal polypeptide induced vasodilatation, showing that some basal vascular tone was present. Nevertheless, the beta 1- and beta 2-agonist isoproterenol had no effect on resistance, and none of the beta-agonists attenuated the pressor responses to alpha-agonists. In conclusion, adrenergic control of nasal mucosal blood flow in seals is essentially exerted through alpha-adrenoceptor-mediated arteriolar constriction, whereas beta-adrenoceptor-mediated dilatation seems to be of little importance. It is suggested that such sympathoadrenergic vascular mechanisms contribute to control nasal heat exchange efficiency in seals.

Animals↗

PubMed1975

Inhibition of pacing-induced coronary dilation by aminophylline.

In closed-chest anaesthetized dogs, aminophylline was infused into the left circumflex coronary artery at a rate of 250 mug/min. When the heart rate was lower than 100 beats/min, infusion did not modify the left circumflex coronary blood flow and resistance. When the heart rate was elevated to an average of 153 +/- 6 beats/min by right atrial pacing, infusion inhibited the increase in left circumflex coronary blood flow and decrease in coronary resistance. The pacing-induced increment in coronary blood flow was reduced by an average of 64% and the flow deficit was associated with a lowering of the coronary sinus blood oxygen tension. Since aminophylline is known to inhibit the coronary dilator action of exogenous adenosine, the results support the concept that adenosine resulting from the breakdown of adenine nucleotides is a mediator of the metabolic regulation of coronary blood flow.

Aminophylline↗

PubMed1976

Systemic and renal hemodynamic effects of bupicomide: a new vasodilator.

The systemic and renal hemodyanmic effects of bupicomide were studied in 10 male patients with uncomplicated essential hypertension of moderate severity. Bupicomide significantly reduced systolic, diastolic, and mean arterial pressure and peripheral vascular resistance and this hypotensive effect was associated with a reflexive increase in heart rate, left ventricular ejection rate, and cardiac index; it had no effect upon other reflexive sympathetic adjustments induced by upright tilt and the Valsalva maneuver. Bupicomide also increased renal blood flow and decreased renal vascular resistance, but it had no effect upon the glomerular filtration rate. The hypotensive mechanism of bupicomide therefore is mediated by peripheral arteriolar dilation, through vascular smooth muscle relaxation. The more immediate clinical side effects of bupicomide are related to its strong vasodialting action and include headaches, cutaneous flushing, and tachycardia.

Clinical Trials as Topic↗

PubMed1976

The effect of amitriptyline on forearm blood flow.

The local effect of intra-arterial infusion of amitriptyline (AT) on forearm blood flow was studied in seven healthy subjects. AT was infused at rates of 0.05, 0.10, 0.15, and 0.20 mg-min--1 for periods of 5 min. Forearm blood flow showed a dose-dependent increase when the dose exeeded 0.10 mg-min--1. On the highest dose level the blood flow increased on an average by 73%. No systemic effects, as reflected by changes in heart rate, blood pressure, and blood flow in the contralateral forearm, were observed during the infusion. The present data indicate a dilatating effect of AT on resistance vessels possibly mediated by an alpha-adrenergic blockade.

Adult↗

PubMed1975

Renal vascular tone in essential and secondary hypertension: hemodynamic and angiographic responses to vasodilators.

The renal vascular response to graded doses of acetylcholine, dopamine and phentolamine, assessed by xenon washout and selective arteriography was used to define the relative contribution of fixed and reversible vascular abnormalities to increased renal vascular resistance in patients with essential or secondary hypertension. The increase in blood flow induced by acetylcholine and dopamine was blunted strikingly in patients with advanced nephrosclerosis, chronic pyelonephritis and polycystic kidney disease and was normal in the kidney contralateral to a significant renal artery stenosis. Conversely, the response to both was potentiated in 9 of 13 (69%) patients with mild essential hypertension. Equivalent potentiation of the response to acetylcholine was induced in normal subjects by increasing renal vascular tone pharmacologically with angiotensin. Phentolamine infused into the renal artery also increased renal blood flow significantly in 6 of 9 (67%) patients with mild essential hypertension, but in none of 15 normal subjects, over a dose reange that paralleled that for alpha-adrenergic blockade. Changes in the selective renal arteriogram were in excellent accord: potentiated response to acetylcholine, phentolamine or dopamine was associated with reversal of the small vessel abnormalities visualized in the arteriogram. The reduced blood flow response in advanced nephrosclerosis or parenchymal disease was associated with a reduced angiographic change during dilator infusion. The results suggest a quantitatively important, functional renal vascular abnormality--perhaps mediated by the sympathetic nervous system--in many patients with mild essential hypertension. Conversely the renal vascular abnormality associated with advanced nephrosclerosis or renal parenchymal disease is largely fixed and is probably due to organic changes.

Acetylcholine↗

PubMed1975

Relationship between adenosine concentration and oxygen supply in rat brain.

Since adenosine is present in normal brain tissue and cerebrosipinal fluid and since it dilates the pial vessels, it is possible that adenosine, in addition to H-+, is also a mediator of the metabolic regulation of cerebral blood flow. Evidence supporting this hypothesis was obtained under various experimental conditions characterized by achange in brain oxygen supply. The brain was frozen in situ by means of a small bonerongeur precooled in liquid N2 and the tissue was processed for adenosine determination (nmol/g of tissue). Electrical stimulation of the cortex at 0, 15, 30, and 45 Hz yielded adenosine levels of 5.4 plus or minus 0.7, 10.5 plus or minus 1.7, 13.0 plusor minus 1.2, and 9.0 plus or minus 2.1 nmol/g. Arterial pressures of 87, 60, and 40mmHg gave adenosine levels of 7.5 plus or minus 0.76, 13 plus or minus 2.6, and 26.6plus or minus 3.3, respectively. Ventilation with 29.7, 20, 10.7, and5.5% O2 significantly increased the adenosine levels to 9.4 plus or minus 3.0, 6.4 plus or minus 1.2, 30.0 plus or minus 9.3, and 63.3 plus or minus 18.2 nmol/g, respectively. Hyperventilation significantly increased adenosine form 6.7 plus or minus 1.0 to 11.8 plus or minus 1.4 nmol/g. This increased adenosine level was reduced by additionof CO2 to the ventilating gas mixture. Lactate, the main H-+ donor, pyruvate, and cAMP changed in a fashion parallel to adenosine. However, cAMP showedonly a small increase in adenosine. These findings are in accordance with the concept that adenosine and H-+ may act synergistally to regulate cerebral blood flow and that endogenous adenosine may exert a small effect on cAMP formation.

Adenosine↗