Biomedical subjects

D Hayoz

Publications and source records attributed to D Hayoz.

At least 73 records · Page 4Linked to original sources

PubMed1997

Age-related changes of the mechanical properties of the carotid artery in spontaneously hypertensive rats.

BACKGROUND: We had previously demonstrated that the distensibility of the carotid artery in spontaneously hypertensive rats (SHR) aged 18 weeks does not differ from that of the carotid artery in normotensive animals for common pressure levels, despite vascular hypertrophy in SHR. OBJECTIVE: To examine the time-course effects of hypertension on the geometry and the mechanical properties of the carotid artery in SHR. METHODS: The mechanical behavior of the carotid arteries of anesthetized SHR, stroke-prone SHR (SHRSP), and Wistar-Kyoto (WKY) rats aged 4, 8, 12, 16, and 32 weeks was examined by simultaneously measuring the internal diameter with an A-mode ultrasonic echo-tracking device and the intra-arterial pressure with a computerized data-acquisition system. Histometric measurements of the carotid artery were performed after death of rats. RESULTS: Blood pressure increased with time in rats of the two genetic hypertensive models. However, it rose earlier and to higher levels in the SHRSP. Cardiac hypertrophy was comparable in the two hypertensive groups whereas vascular hypertrophy was less pronounced in the SHRSP than it was in the SHR. There was an age-related decrease in arterial distensibility in rats of all groups that was more pronounced in the SHRSP than it was in the SHR compared with that in WKY rats (decreases of 57 and 36%, respectively, versus WKY rats aged 32 weeks; P < 0.05). For rats of all ages studied, although aging affected differently the vascular properties of the distinct animal strains, arterial distensibility was increased in the SHR and SHRSP compared with that in control animals for similar blood pressure levels, implying a rightward shift of the distensibility-pressure curves in the two hypertensive models. However, there was a significant reduction in arterial distensibility in rats of the two hypertensive strains at their respective mean blood pressures, compared with that in control animals.

Aging↗

PubMed1997

Synchronous and baroceptor-sensitive oscillations in skin microcirculation: evidence for central autonomic control.

To determine whether skin blood flow is local or takes part in general regulatory mechanisms, we recorded laser-Doppler flowmetry (LDF; left and right index fingers), blood pressure, muscle sympathetic nerve activity (MSNA), R-R interval, and respiration in 10 healthy volunteers and 3 subjects after sympathectomy. We evaluated 1) the synchronism of LDF fluctuations in two index fingers, 2) the relationship with autonomically mediated fluctuations in other signals, and 3) the LDF ability to respond to arterial baroreflex stimulation (by neck suction at frequencies from 0.02 to 0.20 Hz), using spectral analysis (autoregressive uni- and bivariate, time-variant algorithms). Synchronous LDF fluctuations were observed in the index fingers of healthy subjects but not in sympathectomized patients. LDF fluctuations were coherent with those obtained for blood pressure, MSNA, and R-R interval. LDF fluctuations were leading blood pressure in the low-frequency (LF; 0.1 Hz) band and lagging in the respiratory, high-frequency (HF; approximately 0.25 Hz) band, suggesting passive "downstream" transmission only for HF and "upstream" transmission for LF from the microvessels. LDF fluctuations were responsive to sinusoidal neck suction up to 0.1 Hz, indicating response to sympathetic modulation. Skin blood flow thus reflects modifications determined by autonomic activity, detectable by frequency analysis of spontaneous fluctuations.

Adult↗

PubMed1997

Time course changes of the mechanical properties of the carotid artery in renal hypertensive rats.

Distensibility of the carotid artery is not altered 2 weeks after renal artery clipping despite adaptive vascular hypertrophy related to hypertension. The purpose of this study was to assess arterial wall behavior with hypertension persisting for a longer period. Male Wistar rats were examined 1, 5, 9, and 24 weeks after renal artery clipping (two-kidney, one clip renal hypertension; n = 40) or after sham operation (n = 39). Mean blood pressure increased significantly to 132 +/- 4, 143 +/- 4, 153 +/- 4, and 144 +/- 4 versus 98 +/- 2, 107 +/- 2, 115 +/- 3, and 108 +/- 3 mm Hg, respectively, in 1-, 5-, 9-, and 24-week hypertensive rats and age-matched controls. Cardiac and vascular hypertrophy increased in parallel and were correlated to mean blood pressure. Wall stress at mean blood pressure did not differ between the hypertensive and normotensive groups (3.79 +/- 0.24, 4.60 +/- 0.34, 4.49 +/- 0.27, and 4.14 +/- 0.28 versus 3.15 +/- 0.12, 4.14 +/- 0.25, 4.80 +/- 0.28, and 4.69 +/- 0.32 10(3) dyne/cm2, respectively, in 1-, 5-, 9-, and 24-week hypertensive rats and age-matched controls). Distensibility-pressure data from the two groups fell on a common curve for all study periods. The intrinsic properties of the wall constituents were similar in controls and hypertensive rats at 1 and 5 weeks. However, the arteries became stiffer in the 9- and 24-week hypertensive rats, as illustrated by a shift to higher levels of the incremental elastic modulus-stress curve. Wall stress remains constant at mean blood pressure as a result of the increase in wall tissue mass. With time, even though the distensibility-pressure curve is not shifted downward, the thickened wall becomes stiffer in the hypertensive rats, which may predispose them to accelerated alterations of the wall material.

Animals↗

PubMed1997

Effects of SR 49059, a new orally active and specific vasopressin V1 receptor antagonist, on vasopressin-induced vasoconstriction in humans.

We have evaluated the efficacy of SR 49059, a new orally active and specific vasopressin V1 receptor antagonist (arginine-vasopressin [AVP]), in the blockade of the vascular effects of exogenous AVP in healthy subjects. In preliminary experiments, two procedures to measure the V1 vascular effects of AVP were assessed. First, the AVP-induced changes in skin blood flow were investigated by the injection of increasing doses of AVP intradermally, with or without a previous local vasodilation with calcitonin gene-related peptide (CGRP). In a second protocol, AVP was infused intra-arterially, and the changes in radial artery diameter and blood flow were measured. The intradermal injection of AVP caused significant decreases in skin blood flow, and the use of CGRP increased the sensitivity of the method by a factor of 10(2) to 10(3). AVP infused intra-arterially caused dose-dependent decreases in the radial artery diameter and blood flow. In the main study, the potency and efficacy of SR 49059 to block the AVP-induced changes in skin blood flow were assessed in 12 healthy men with a double-blind, triple crossover study design. The subjects were randomized to receive a placebo orally and 30 mg and 300 mg of the antagonist at a 1-week interval. The subjects were then further randomized to evaluate the efficacy of the same doses of the antagonist to block the vasoconstriction of the radial artery induced by an intra-arterial infusion of AVP. SR 49059 inhibits, dose-dependently and significantly, the AVP-induced changes in skin blood flow, with a peak effect occurring between 2 and 6 hours after injection. In addition, the 300-mg dose of SR 49059 completely blocked the vasoconstriction of the radial artery induced by AVP. In conclusion, skin blood-flow measurement, after intradermal injection of AVP on a skin area vasodilated with CGRP, is an effective method to investigate the V1 vascular effect of AVP in humans. SR 49059 is a potent and specific antagonist of V1 receptors, which blocks the AVP-induced vasoconstriction.

Administration, Oral↗

PubMed1997

Acute inflammatory reaction associated with endoluminal bypass grafts.

PURPOSE: Nonspecific inflammatory reactions characterized by local tenderness, fever, and flu-like discomfort have been seen in patients undergoing endoluminal graft placement in the abdominal aorta or the femoral arteries. We undertook a study to assess the clinical and laboratory parameters of this inflammation. METHODS: Ten patients with femoropopliteal artery (n = 9) or aortic (n = 1) lesions were treated with EndoPro System 1 stent-grafts made of nitinol alloy and covered with a polyester (Dacron) fabric. Eleven patients implanted with a bare nitinol stent served as the control group. RESULTS: In the stent-graft group, four patients showed clinical signs of acute inflammation manifested by fever and local tenderness. Three of these patients suffered thrombosis of the stent-grafts during the first month of follow-up. Plasma levels of interleukin-1 beta and interleukin-6 in all stent-graft patients were markedly increased 1 day after intervention (7.3 +/- 2.8 versus 90.2 +/- 34.1 pg/mL and 15.6 +/- 5.8 versus 175.5 +/- 66.3 pg/mL, respectively; p < 0.01). This was followed by an increase in fibrinogen (3.0 +/- 0.2 versus 5.0 +/- 0.2 g/L; p < 0.05) and C-reactive protein (14.6 +/- 3.3 versus 77.5 +/- 15.0 mg/L; p < 0.01) at 1 week. No direct correlation between the inflammatory markers and symptoms could be found. In vitro analysis showed that individual components of the stent-graft did not activate human neutrophils, whereas the intact stent-graft itself induced a marked neutrophil activation. CONCLUSIONS: The component of the self-expanding stent-graft responsible for the nonspecific inflammatory reaction was not identified in this study. It is likely that the stent-graft itself or some as yet unrecognized element of the device other than the Dacron fabric or metal alloy may be a potent in vivo inducer of cytokine reaction by neutrophils.

Aged↗

PubMed1997

Heterogeneous vascular response to vasopressin: radial artery versus forearm blood flow.

BACKGROUND: Arginine vasopressin (AVP) administered intra-arterially to normal volunteers exerts a biphasic effect on forearm blood flow when the effect is extrapolated from plethysmographic measurements. OBJECTIVE: To assess whether the high-dose AVP-induced increase in forearm blood flow could be confirmed when calculating blood flow from continuous radial artery diameter and flow velocity recordings obtained by using a high-resolution echotracking device combined with a Doppler system. METHODS: Increasing doses (0.04-0.8 ng/kg per min) of AVP were infused into a brachial artery of seven normal male volunteers (aged 21-33 years). Forearm blood flow derived from venous occlusion plethysmography was assessed simultaneously with proximal radial artery blood flow calculated from luminal area and flow velocity measurements. RESULTS: Confirming previous reports, plethysmography showed an increase in global forearm blood flow by > 100% with AVP concentrations > or = 0.2 ng/kg per min. In contrast, direct measurements of lumen diameter and blood flow velocity in the radial artery revealed a marked dose-dependent vasoconstriction with a > 30% decline in blood flow at the highest AVP concentration. CONCLUSIONS: The discrepancy between the two measurements suggests that AVP has a dual effect on forearm haemodynamics. At high AVP concentration, the muscle blood flow increase predominates over the vasoconstriction in the skin circulation. Furthermore, this study strongly suggests a heterogeneity of the vascular response to vasomediators by showing that opposing responses exist not only between resistive and conduit vessels but also between conduit arteries of a common vascular bed.

Adult↗

PubMed1997

Remodelling of conduit arteries in hypertension: special emphasis on the mechanical and metabolic consequences of vascular hypertrophy.

Vascular remodelling is well demonstrated in both human and experimental hypertension. Whether it develops in response to high blood pressure or as a marker of hypertension independently of any pressure level, it contributes in resistance arteries to maintaining an elevated blood pressure. Only recently, with the development of sensitive and reproducible methods, has remodelling of conduit arteries been assessed. A high resolution B-mode ultrasound technique can be used to measure arterial wall thickness and luminal dimension during the cardiac cycle. Changes in geometry and structure of conduit vessels have been observed in hypertensive patients or during experimental studies in animal models of hypertension. These changes may influence the buffering capacity of the conduit vessels, resulting in alteration of the dynamic component of the vascular impedance. Reduction of the systemic compliance may increase afterload and with time depress cardiac function. Ultrasonography apparatus is designed to measure local elastic properties and structural alterations and should be considered as such. Indeed, extrapolation of data acquired at a given arterial site to other parts of the vascular bed is hazardous. There exist other indirect methods based on pulse wave contour analysis and pulse wave velocity that can estimate global arterial compliance. Unfortunately, these methods have other limitations that restrict their use. Because conduit vessels represent one of the most important targets for pressure-induced lesions, namely atherosclerosis, they may be viewed as a surrogate endpoint in hypertension. Do we have evidence that vascular remodelling associated with hypertension predisposes to accelerated atherosclerosis? The purpose of this paper is to discuss the evidence that may support such a concept.

Arteries↗

PubMed1996

Progressive withdrawal of muscle nerve sympathetic activity preceding vaso-vagal syncope during lower-body negative pressure.

We report the observation of a vaso-vagal syncope (VVS) occurring during lower body negative pressure in a young male volunteer. Recording of the peripheral blood flow, blood pressure and muscular sympathetic nerve activity revealed first a progressive withdrawal of muscle nerve sympathetic activity with redistribution of blood flow before the onset of the VVS.

Adult↗

PubMed1996

Contributions of vascular tone and structure to elastic properties of a medium-sized artery.

Isobaric compliance and distensibility of the radial artery were recently reported to be normal or slightly increased in untreated hypertensive patients. However, these findings provide no information on the intrinsic mechanical properties of the wall material. To address this question, we determined intima-media wall thickness, wall-to-lumen ratio, and incremental elastic modulus in the radial artery of 25 untreated hypertensive patients with blood pressure of 150 +/- 14/103 +/- 6 mm Hg (mean +/- SD) and 25 matched control subjects with blood pressure of 118 +/- 9/79 +/- 6 mm Hg. High-resolution echotracking for assessment of internal diameter and intima-media wall thickness was combined with measurements of blood flow velocity by Doppler and blood pressure by photoplethysmography. In addition, isobaric compliance and distensibility and incremental elastic modulus were measured at peak diameter during reactive hyperemia after a 5-minute brachial occlusion. No significant difference was found between the two groups for isobaric compliance or distensibility at baseline or during hyperemia. However, incremental elastic modulus at 100 mg Hg tended to be lower in hypertensive patients than control subjects (1.9 +/- 1.1 versus 2.5 +/- 1.2 mm Hg x 10(4), P = .1) in resting conditions. Hypertensive patients and control subjects had similar internal diameters (2.47 +/- 0.32 versus 2.41 +/- 0.35 microm), but intima-media wall thickness and wall-to-lumen ratio were significantly increased in hypertensive patients compared with control subjects (0.268 +/- 0.032 versus 0.236 +/- 0.025 mm -P < or = .01- and 0.220 +/- 0.038 versus 0.195 +/- 0.028 -P < or = .05-, respectively). Peak hyperemic blood flow response (hypertensive patients versus control subjects: 349% versus 360% increase from baseline) and reactive hyperemic dilation (7.2% versus 7.9%) were similar in amplitude and duration in the two groups. These results suggest that wall thickening is an adaptive process that reduces wall tension in hypertensive patients while preserving a normal mechanical behavior of the radial artery. This is most likely accomplished by modification of the incremental elastic modulus of wall components rather than by a change in vascular tone.

Adult↗

PubMed1995

[Noninvasive assessment of morphology and function of the great vessels].

Hypertension is well recognized as a risk factor that is associated with an increased incidence of stroke and myocardial infarction. The early detection of atherosclerosis is a real challenge and should be carried on at a cost and with a degree of risk and invasiveness that does not preclude its use in subjects with cardiovascular risk factors. For this purpose we have developed a non-invasive approach using a high resolution echotracking device making it possible to measure internal diameter and wall thickness of conduit arteries as well as their biomechanical properties. We present here a methodological overview of the system with a brief clinical study addressing the biomechanical properties of a medium size artery in hypertension as compared with normotension.

Arteries↗

PubMed1995

Simultaneous ipsilateral and contralateral measurements of vasomotion in conduit arteries of human upper limbs.

We investigated the patterns of vasomotion in various conduit arteries of the human arm. The internal diameter of the brachial, radial, ulnar, and digital artery was measured noninvasively in 17 healthy volunteers (aged 24-40 yr), using a high-precision ultrasonic echotracking device. Under resting conditions, the radial, ulnar, and digital internal diameter exhibited spontaneous oscillations (vasomotion) with a relative amplitude ranging from 1 to 5% of the mean diameter and a fundamental frequency ranging from 0.01 to 0.05 Hz. This oscillatory behavior was either quasi-periodic or irregular. The low-frequency mode (f < or = 0.05 Hz) present in the diameter signal was identified neither in the heart rate nor in the blood pressure signal. To determine whether the oscillatory activity was propagative, simultaneous measurements of diameter at two sites on the right radial artery were performed and revealed no significant consistent phase shift. Ipsilateral radial and ulnar diameters, measured at the wrist level, exhibited similar and synchronous vasomotion patterns, despite differences in the amplitude. For all subjects, contralateral measurements, performed at two symmetrical sites of the radial arteries, showed similar oscillatory patterns with a strong correlation (0.85 < r < 0.99, n = 12). These results suggested the existence of a global regulatory mechanism that coordinates vasomotion in the large conduit arteries of the human arm.

Adult↗

PubMed1995

Prevention of vascular remodelling in cardiovascular disease.

The early detection of arterial wall transformations that may further evolve into atherosclerosis may help to identify high-risk patients among the hypertensive population and to select the most appropriate treatment. Intima-media layer thickening that affects a number of hypertensive subjects may potentially represent an indicator of accelerated atherosclerotic transformation of the vessel wall. Diagnosis and quantification of these early changes preceding plaque development should make it possible to determine whether antihypertensive treatment can restore normal wall structures in addition to normalizing the blood pressure. This article reviews some of the new approaches developed in our laboratory to assess both structure and function of conduit vessels. Preliminary data suggest that it is feasible to identify minute geometrical changes in hypertensive subjects long before major vascular lesions occur. This opens a whole new field of investigation into early arterial remodelling, a potential precursor of atherosclerosis.

Adaptation, Physiological↗

PubMed1995

Flow-diameter phase shift. A potential indicator of conduit artery function.

This study assesses (1) the relation of the very-low-frequency vasomotion (< 0.02 Hz) of the radial artery of young healthy volunteers to regional blood flow and (2) its distribution in the upper extremities. Radial artery diameters from comparable sites were measured on contralateral extremities in 18 young healthy volunteers by an echo tracking system simultaneously with blood flow velocity determined by continuous wave Doppler and blood pressure acquired by photoplethysmography in the middle finger. A synchronous global pattern of vasomotion was detected on contralateral radial arteries, suggesting the presence of either a centrally located pacemaker or a humoral system. Modulation of sympathovagal balance in 8 subjects did not significantly alter either the frequency or amplitude of the very-low-frequency vasomotor waves. Matching patterns of diameter and flow oscillations of the very-low-frequency type recorded at the same site were obtained in 10 strictly nonsmoking volunteers for given periods of time. A consistent phase lag was observed between flow and diameter signals. Flow always preceded the diameter fluctuations by a mean (+/- SEM) course of 20.8 +/- 1.56 seconds. Although the physiological basis for oscillatory behavior remains for the moment highly speculative, these results suggest that the very-low-frequency vasomotion pattern in this conduit vessel might be a flow- or shear stress-dependent phenomenon. Shear stress changes at the endothelium modulate vascular tone through the release of vasodilators. The noninvasive assessment of the diameter-flow relation may thus offer a new way of addressing vascular wall function in medium-sized and large arteries in subjects with cardiovascular risk factors.

Adult↗

PubMed1995

Chronic nitric oxide synthase inhibition and carotid artery distensibility in renal hypertensive rats.

The goal of the present study was to examine the viscoelastic properties of the carotid artery in genetically identical rats exposed to similar levels of blood pressure sustained by different mechanisms. Eight-week old male Wistar rats were examined 2 weeks after renal artery clipping (two-kidney, one clip [2K1C] Goldblatt rats, n = 53) or sham operation (n = 49). One half of the 2K1C and sham rats received the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 1.48 mmol/L) in their drinking water for 2 weeks after the surgical procedure. Mean blood pressure increased significantly in the 2K1C-water (182 mm Hg), 2K1C-L-NAME (197 mm Hg), and sham-L-NAME (170 mm Hg) rats compared with the sham-water rats (127 mm Hg). Plasma renin activity was not altered by L-NAME but significantly enhanced after renal artery clipping. A significant and similar increase in the cross-sectional area of the carotid artery was observed in L-NAME and vehicle-treated 2K1C rats. L-NAME per se did not modify cross-sectional area in the sham rats. There was a significant upward shift of the distensibility-pressure curve in the L-NAME- and vehicle-treated 2K1C rats compared with the sham-L-NAME rats. L-NAME treatment did not alter the distensibility-pressure curve in the 2K1C rats. These results demonstrate that the mechanisms responsible for artery wall hypertrophy in renovascular hypertension are accompanied by an increase in arterial distensibility that is not dependent on the synthesis of nitric oxide.

Amino Acid Oxidoreductases↗

PubMed1995

Postischemic blood flow response in hypercholesterolemic patients.

We undertook this cross-sectional study to compare the mechanical behavior and postischemic response of the radial artery of 15 newly diagnosed hypercholesterolemic patients with those of 15 age- and sex-matched normocholesterolemic control subjects and 21 hypercholesterolemic patients treated for 2 years with an 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (simvastatin, 10 to 20 mg/d). At the time of the study total cholesterol levels were at 7.9 +/- 0.2, 4.9 +/- 0.2, and 6.0 +/- 0.3 mmol/L in the three groups, respectively (mean +/- SEM, P < .001). High-resolution, noninvasive echotracking for assessment of internal arterial diameter was combined with measurements of blood flow velocity by Doppler and blood pressure by photoplethysmography. Radial cross-sectional compliance and distensibility were similar in all groups. Forearm blood flow and flow-mediated dilation were measured after a 5-minute upper arm occlusion. Flow was calculated from the vessel diameter and blood flow velocity recorded simultaneously at the same site. Flow-mediated dilation after ischemia was not significantly different among the three groups. However, forearm blood flow increase was markedly blunted (P < .01) in untreated hypercholesterolemic patients (211%) compared with the normocholesterolemic control subjects (411%) and treated patients (365%). These findings suggest that the distensibility of the radial artery, a muscular conduit vessel usually devoid of atherosclerotic lesions, and its flow-mediated dilation are preserved in hypercholesterolemic patients. In contrast, forearm resistance vessels exhibit a markedly reduced postischemic blood flow response that may be restored by prolonged lipid-lowering intervention.

Adult↗

PubMed1994

[Increased vascular sensitivity to nitroglycerin in patients with hypercholesterolemia and peripheral endothelial dysfunction].

The effects of the endothelium-dependent vasodilator acetylcholine, the endothelium-independent vasodilator nitroglycerin and a drug which inhibits basal nitric oxide (NO) release (L-NG-monomethyl-arginine [L-NMMA]) on the diameter of the radial artery and blood flow were studied in eight patients with hypercholesterolaemia (total cholesterol: 280 +/- 9 mg/dl, age 54 +/- 3 years) and eight healthy subjects of the same age (total cholesterol 197 +/- 12 mg/dl, age 51 +/- 4 years). Arterial diameter was measured by a recently developed high resolution ultrasound technique. Increasing concentrations of acetylcholine (10(-8) to 10(-6) mol/l) produced dose-dependent increases in flow rate in the healthy subjects (maximum +150% +/- 6% at 10(-6) mol/l), but much less in the patients with hypercholesterolaemia (+24% +/- 12%). L-NMMA caused comparable reductions in forearm blood flow in both groups. Nitroglycerin increased blood flow in the hypercholesterolaemia group to a significantly greater extent (+370% +/- 69%) than in the controls (+145 +/- 62%). The effects of acetylcholine, L-NMMA and nitroglycerin on radial artery diameter did not differ significantly between the two groups. The poor response (in terms of blood flow) to acetylcholine in the hypercholesterolaemia group points to an endothelial dysfunction in the arterial microcirculation. The fact that L-NMMA caused similar reductions in forearm blood flow in the controls and hypercholesterolaemia patients alike shows that basal NO synthase activity must be comparable in the two groups and therefore cannot be held responsible for the endothelial dysfunction. This endothelial dysfunction is linked with increased responsiveness to the endothelium-independent vasodilator nitroglycerin.

Acetylcholine↗

PubMed1994

Long-term nitric oxide synthase inhibition and distensibility of carotid artery in intact rats.

The goal of the present study was to evaluate the effect of long-term nitric oxide synthase inhibition by NG-nitro-L-arginine-methyl ester (L-NAME) on the morphology and viscoelastic properties of the carotid arteries in rats. Twelve-week-old Wistar-Kyoto rats were treated for 6 weeks with either the nitric oxide synthase inhibitor L-NAME (0.4 g/L in drinking water; L-NAME rats, n = 13) or tap water (control rats, n = 13). Age-matched spontaneously hypertensive rats (SHR, n = 14) received tap water for the same period. The internal diameter of the common carotid artery was measured continuously with an echo-tracking device with the rats under anesthesia with halothane. Intra-arterial pressure was monitored on the contralateral side. L-NAME rats exhibited arterial pressures similar to those of SHR. The distensibility pressure-curve determined in L-NAME rats was a direct continuation of that obtained in control rats. In contrast the distensibility in SHR was increased (P < .01, SHR versus L-NAME rats). Carotid artery cross-sectional area and left ventricular weight index were increased similarly in SHR and L-NAME rats compared with control rats. Thus the hypertension caused by long-term nitric oxide synthesis inhibition was not associated with the increased arterial distensibility observed in SHR despite similar blood pressure elevations, similar arterial hypertrophy, and consequently similar wall stress. This suggests a role for nitric oxide in regulating the mechanical behavior of arteries exposed to high blood pressure.

Amino Acid Oxidoreductases↗

PubMed1994

Endothelial dysfunction in chronic heart failure. Experimental and clinical studies.

The endothelium plays an important role in the control of human vascular tone by releasing endothelium-derived nitric oxide. Therefore, endothelial dysfunction could be involved in the increased peripheral vasoconstriction of patients with chronic congestive heart failure (CHF). To investigate endothelial function in humans in vivo, agents such as acetylcholine are used to stimulate the release of endothelium-derived nitric oxide (EDRF). Conversely, N-mono-methyl-L-arginine (L-NMMA), a specific inhibitor of nitric oxide synthesis from L-arginine decreases forearm blood flow by inhibiting the basal release of nitric oxide. Consistent with experimental studies, the blood flow response to acetylcholine is blunted in patients with chronic heart failure as compared to healthy age-matched volunteers. In contrast, the decrease in blood flow induced by L-NMMA appears to be exaggerated in CHF. The blood flow response to nitroglycerin or sodium nitroprusside, endothelium-independent vasodilators, is usually preserved in patients with chronic, non-edematous heart failure, indicating a normal response of the vascular smooth muscle of resistance vessels to exogenous nitric oxide. In contrast, the dilator response of the radial artery diameter to nitroglycerin and flow-dependent dilation are impaired in patients with chronic heart failure, indicating that the abnormal flow-mediated relaxation of large arteries may be due to both endothelial and vascular smooth muscle alterations. Thus, impaired endothelium-dependent dilation of peripheral resistance vessels emerges in chronic heart failure, suggesting a reduced release of nitric oxide upon stimulation. Thus, endothelial dysfunction may be involved in the impaired vasodilator capacity in the peripheral circulation, e.g. during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Arginine↗