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Robinson Joannides

Publications and source records attributed to Robinson Joannides.

9 recordsLinked to original sources
PubMed2007

AT1 receptor blockade prevents the decrease in conduit artery flow-mediated dilatation during NOS inhibition in humans.

Whether AT(1) (angiotenin II type 1) receptor blockade can prevent the decrease in conduit artery FMD (flow-mediated dilatation) during NOS (nitric oxide synthase) inhibition by alternative endothelial pathways has not been explored previously in humans. In 12 healthy subjects, we measured radial artery diameter (echotracking) and flow (Doppler) during FMD induced by sustained reactive hyperaemia during a control period and following NOS inhibition [1.5 mg.min(-1).l(-1) L-NMMA (N(G)-monomethyl-L-arginine)], after a single oral administration of telmisartan (80 mg) or placebo, using a randomized double-blind cross-over design. In six volunteers, we also assessed the roles of prostacyclin and EDHF (endothelium-derived hyperpolarizing factor) during radial FMD after AT(1) receptor blockade by oral administration of aspirin (500 mg) alone, aspirin+L-NMMA or aspirin+L-NMMA+fluconazole (a cytochrome epoxygenases inhibitor; 0.37 mg.min(-1).l(-1)). Telmisartan did not affect radial artery FMD in the control period (10.9+/-0.6% with placebo compared with 9.9+/-0.7% with telmisartan), but prevented its decrease after L-NMMA (9.3+/-0.8% with placebo compared with 12.6+/-1.2% with telmisartan; P<0.05) with no modification in baseline parameters, hyperaemia and radial artery endothelium-independent dilatation to sodium nitroprusside. Moreover, in telmisartan-treated subjects, radial artery FMD, compared with control (9.0+/-1.0%), was not modified by aspirin alone (9.4+/-0.7%) or associated with L-NMMA (9.5+/-0.5%), but was reduced by the combination of aspirin, L-NMMA and fluconazole (7.5+/-0.6%; P<0.05). These results demonstrate that AT(1) receptor blockade prevents the decrease in conduit artery FMD during NOS inhibition in humans, suggesting the development of a compensatory endothelial mechanism. This mechanism appears to be independent of prostacyclin and could possibly be related to an EDHF release.

Adult↗
PubMed2006

Crucial role of NO and endothelium-derived hyperpolarizing factor in human sustained conduit artery flow-mediated dilatation.

Whether NO is involved or not in sustained conduit artery flow-mediated dilatation in humans remains unclear. Moreover, the role of endothelium-derived hyperpolarizing factor (EDHF), synthesized by cytochrome epoxygenases and acting through calcium-activated potassium channels, and its relationship with NO during flow-mediated dilatation have never been investigated previously. In 12 healthy subjects we measured radial artery diameter (echotracking) and blood flow (Doppler) during flow-mediated dilatation induced by gradual distal hand skin heating (34 to 44 degrees C), during the local infusion of saline and inhibitors of NO synthase (N(G)-monomethyl-l-arginine [l-NMMA]: 8 to 20 micromol/min per liter), calcium-activated potassium channels (tetraethylammonium chloride: 9 micromol/min per liter), and cytochrome epoxygenases (fluconazole: 0.4 to 1.6 micromol/min per liter), alone and in combination. Mean wall shear stress, the flow-mediated dilatation stimulus, was calculated at each level of flow, and the diameter-wall shear stress relationship was constructed. During heating, compared with saline, the diameter-shear stress relationship was shifted downward by l-NMMA, tetraethylammonium, fluconazole, and, in a more pronounced manner, by the combinations of l-NMMA with tetraethylammonium or with fluconazole. Therefore, maximal radial artery flow-mediated dilatation, compared with saline (0.62+/-0.03 mm), was decreased under our experimental conditions by l-NMMA (-39+/-4%), tetraethylammonium chloride (-14+/-4%), fluconazole (-18+/-6%), and to a greater extent, by the combinations of l-NMMA with tetraethylammonium (-64+/-4%) or with fluconazole (-71+/-3%). This study demonstrates that NO and a cytochrome-related EDHF are involved in peripheral conduit artery flow-mediated dilatation in humans during sustained flow conditions. Moreover, the synergistic effects of the inhibitors strongly suggest a functional interaction between NO and EDHF pathways.

Adult↗
PubMed2006

Brachial pressure-independent reduction in carotid stiffness after long-term angiotensin-converting enzyme inhibition in diabetic hypertensives.

Hypertension and diabetes are associated with an increased arterial stiffness. A direct blood pressure-independent effect of angiotensin-converting enzyme inhibitors on arterial stiffness has never been unequivocally demonstrated. In this mechanistic study, we used an experimental design in which patients responding to 1 month treatment with 4 mg perindopril were randomized double-blind to either 4 mg perindopril or 8 mg perindopril for 6 months. We determined carotid distensibility with echotracking and applanation tonometry at baseline and after the 7-month treatment period in 57 essential hypertensive patients with type 2 diabetes (age 63+/-7 years). We monitored ambulatory blood pressure at baseline and after treatment. After 7 months treatment, 24-hour ambulatory blood pressure significantly decreased, with no significant difference between 4 mg and 8 mg perindopril. Carotid distensibility increased more after 8 mg perindopril compared with 4 mg perindopril (8 mg: from 13.1+/-5.9 to 16.0+/-6.7 kPa(-1)x10(-3); 4 mg: from 13.2+/-5.2 to 12.7+/-5.9 kPa(-1)x10(-3); ANOVA, dose-period interaction, P<0.05). Carotid internal diameter and elastic modulus were significantly lower after 8 mg perindopril compared with 4 mg perindopril, independent of blood pressure reduction. These results indicate a dose-dependent and blood pressure-independent reduction in carotid stiffness under chronic treatment with an angiotensin-converting enzyme inhibitor. They suggest that arterial distensibility was increased through an inward remodeling, leading to a reduction in wall stress, thus reducing elastic modulus. They also suggest that long-term administration of high doses (8 mg) of perindopril is required to improve carotid structure and function in hypertensive patients with type 2 diabetes.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2006

Comparative effects of ivabradine, a selective heart rate-lowering agent, and propranolol on systemic and cardiac haemodynamics at rest and during exercise.

AIM: To compare in humans the effects of ivabradine and propranolol on cardiac and systemic haemodynamics at rest, during tilt and exercise. METHODS: Nine healthy volunteers randomly received single oral doses of ivabradine (Iva, 30 mg), propranolol (Propra, 40 mg) or placebo (Plac) during a double-blind cross-over study. Doses were selected to be equipotent in heart rate (HR) reduction. HR, systolic and diastolic blood pressure (SBP, DBP), cardiac index (CI, bioimpedance), rate pressure product (RPP), plasma epinephrine (E) and norepinephrine (NE), were measured at rest at baseline, before and after two tilt and exercise tests, started 2 and 5 h after drug intake. Heart rate variability (low to high frequency ratio LF/HF) was evaluated at rest and at 5 th minute of tilt. RESULTS: At rest, HR and RPP decreased similarly with Iva and Propra (both P < 0.01). During tilt, HR increased less with Iva than Propra (P < 0.01), LF/HF decreased after Iva (P < 0.03), SBP and mean blood pressure decreased after Propra (both P < 0.01), RPP decreased similarly after Iva and Propra (both P < 0.01) and CI decreased to a greater extent with Propra than with Iva or Plac (both P < 0.04). During exercise, Iva and Propra similarly decreased HR (both P < 0.01) and RPP (P < 0.01). CONCLUSIONS: These results demonstrate that for a similar decrease in HR at rest and during sympathetic stimulation, acute administration of ivabradine, a selective heart rate-lowering agent, decreased myocardial oxygen demand to the same extent as a reference beta-blocker, propranolol, but without evidence of depressant effect on cardiac function.

Adolescent↗
PubMed2006

Clinical methods for the evaluation of endothelial function-- a focus on resistance arteries.

Endothelial dysfunction is a key event in the pathophysiology of cardiovascular diseases and appears as a strong independent predictor of cardiovascular events. In this context, biological evaluation of endothelial circulating markers can be helpful. However, functional tests using pharmacological stimuli appear more specific for the study of resistance arteries. These methods consist in the evaluation of the endothelium-dependent changes in regional vascular flow in response to local infusion of substances that act through endothelial receptors without modification of systemic arterial pressure and in comparison with a non endothelium-dependent relaxation. Flow is measured by Doppler and intravascular ultrasound in coronary circulation, laser Doppler in skin and by venous occlusion plethysmography in peripheral muscular arteries. Similar studies can be performed ex vivo using isolated resistance arteries obtained from fat subcutaneous biopsies. In addition, other information can be obtained from reactive hyperemia and the study of the flow-mediated dilatation of conduit arteries to enable a selective and comprehensive approach of the heterogeneity of endothelial function in pathophysiology.

Acetylcholine↗
PubMed2005

Evidence for a basal release of a cytochrome-related endothelium-derived hyperpolarizing factor in the radial artery in humans.

Whether a cytochrome P-450 (CYP)-related endothelium-derived hyperpolarizing factor (EDHF), acting through calcium-activated potassium (K(Ca)) channels, interacts with nitric oxide (NO) to regulate the basal diameter of human peripheral conduit arteries is unexplored in vivo. Radial artery diameter (echo tracking) and blood flow (Doppler) were measured, after oral aspirin (500 mg), in eight healthy volunteers during local infusion for 8 min of tetraethylammonium chloride (TEA; 9 micromol/min), as K(Ca) channel inhibitor, and fluconazole (0.4 micromol/min), as CYP inhibitor, alone and in combination with N(G)-monomethyl-L-arginine (L-NMMA; 8 micromol/min), as endothelial NO synthase inhibitor. Endothelium-independent dilatation was assessed by using sodium nitroprusside (SNP). Radial diameter was unaffected by L-NMMA (0.4 +/- 0.9%) and fluconazole (-1.6 +/- 0.8%) but was decreased by TEA (-5.0 +/- 1.0%), L-NMMA + fluconazole (-5.3 +/- 0.5%), and L-NMMA + TEA (-9.9 +/- 1.3%). These effects are still significant even when the concomitant decreases in blood flow induced by L-NMMA (-24 +/- 4%), TEA (-21 +/- 3%), L-NMMA + fluconazole (-26 +/- 5%), and L-NMMA + TEA (-35 +/- 4%) were taken as covariate into analysis. Conversely, fluconazole alone slightly but not significantly increased radial flow (13 +/- 6%). L-NMMA alone or with TEA and with fluconazole enhanced radial artery dilatation to SNP, whereas TEA and fluconazole alone did not modify this response. These results confirm in humans the involvement of NO and K(Ca) channels in the regulation of basal conduit artery diameter. Moreover, the synergistic effect of combined inhibition of NO synthesis and CYP on the decrease in radial diameter in the absence of such effect after L-NMMA and fluconazole alone unmasks the role of CYP in this regulation and shows the presence of an interaction between NO and a CYP-related EDHF to maintain peripheral conduit artery diameter in vivo. Furthermore, the higher vasoconstrictor effect of TEA compared with fluconazole suggests that different K(Ca) channel-dependent hyperpolarizing mechanisms could exist in conduit arteries.

Adult↗
PubMed2005

Calcium-activated potassium channels and NO regulate human peripheral conduit artery mechanics.

The role of NO in the regulation of the mechanical properties of conduit arteries is controversial in humans, and the involvement of an endothelium-derived hyperpolarizing factor (EDHF), acting through calcium-activated potassium (KCa) channels, has never been investigated at this level in vivo. We assessed in healthy volunteers, after oral administration of aspirin (500 mg), the effect of local infusion of NG-monomethyl-L-arginine (L-NMMA; 8 mumol/min for 8 minutes), an NO synthase inhibitor, tetraethylammonium chloride (TEA; 9 mumol/min for 8 minutes), a KCa channels inhibitor, and the combination of both on radial artery internal diameter, wall thickness (echo tracking), blood flow (Doppler), and pressure. The incremental elastic modulus and compliance were fitted as functions of midwall stress. L-NMMA decreased modulus and increased compliance at high levels of midwall stress (all P<0.05) without affecting radial diameter. TEA reduced radial diameter from 2.68+/-0.07 to 2.50+/-0.08 10(-3) m, increased the modulus, and decreased the compliance at all levels of stress (all P<0.05). Combination of both inhibitors synergistically enhanced the increase in modulus, the decrease in diameter (from 2.71+/-0.10 to 2.42+/-0.09 10(-3) m), and compliance compared with TEA alone (all P<0.05). These results confirm that inhibition of NO synthesis is associated with a paradoxical isometric smooth muscle relaxation of the radial artery. They demonstrate the involvement of KCa channels in the regulation of the mechanical properties of peripheral conduit arteries, supporting a role for EDHF at this level in vivo. Moreover, the synergistic effect of l-NMMA and TEA shows that KCa channels compensate for the loss of NO synthesis to maintain peripheral conduit artery diameter and mechanics.

Adult↗
PubMed2002

Influence of vascular dimension on gender difference in flow-dependent dilatation of peripheral conduit arteries.

To assess the influence of initial diameter on the gender difference in flow-dependent dilatation (FDD) of the conduit artery, we measured radial artery internal diameter (echotracking), flow (Doppler) and total blood viscosity in 24 healthy (25 +/- 0.8 yr) men and women during reactive hyperemia (RH) and during a gradual hand skin heating (SH). At baseline, mean diameter (men, 2.76 +/- 0.09 vs. women, 2.32 +/- 0.07 mm, P < 0.05), flow (men, 21 +/- 4 vs. women, 10 +/- 1 ml/min, P < 0.05), and blood viscosity (men, 4.13 +/- 0.07 vs. women, 3.92 +/- 0.13 cP, P < 0.05) were higher in men but mean shear stress (MSS) was not different between groups. During RH, the percent increase in diameter was lower in men (men, 9 +/- 1 vs. women, 13 +/- 1%, P < 0.05). This difference was suppressed after correction for baseline diameter. During SH, the increase in diameter with flow was higher in women (P < 0.01). However, the increase in MSS was higher in women because of their smaller diameter at each level of flow (P < 0.01) and there was no difference between groups for the increase in diameter at each level of MSS. These results demonstrate in a direct manner that initial diameter influences the magnitude of FDD of conduit arteries in humans by modifying the value of the arterial wall shear stress at each level of flow and support the interest of the heating method in presence of heterogeneous groups.

Analysis of Variance↗