| 1. |
- Johansson, Kristina, et al.
(författare)
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Effects of blockade of alpha- and beta-adrenoceptors and neuropeptide Y(1) receptors, as well as brachial plexus blockade, on endothelium-dependent vasodilation in the human forearm
- 2002
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Ingår i: Clinical and experimental pharmacology & physiology. - : Wiley. - 0305-1870 .- 1440-1681. ; 29:7, s. 603-607
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Tidskriftsartikel (refereegranskat)abstract
- 1. The aim of the present study was to investigate the effects of alpha-adrenoceptor blockade (phentolamine), beta-adrenoceptor blockade (propranolol), neuropeptide Y(1) receptor blockade and neurogenic blockade (brachial plexus) on endothelium-dependent vasodilation (EDV) in the human forearm. 2. Forty-four young healthy volunteers underwent forearm blood flow (FBF) measurements, using venous occlusion plethysmography, during local intra-arterial infusions of methacholine (MCh; inducing EDV) and sodium nitroprusside (SNP; inducing endothelium-independent vasodilation (EIDV)). These measurements were undertaken at baseline and were repeated with either concomitant local intra-arterial infusion of phentolamine (n = 8), propranolol (n = 7) or saline (n = 6) in the forearm, neuropeptide Y(1) receptor blockade (n = 12) given i.v. or during axillary plexus blockade (n = 11). 3. Both alpha-adrenoceptor blockade and neurogenic blockade induced an upward shift in the dose-response curve for both EDV and EIDV. beta-Adrenoceptor blockade did not change resting FBF or EIDV, but induced a significant decrease in EDV (P = 0.015). Neuropeptide Y(1) receptor blocker induced no significant changes in resting FBF, EDV and EIDV and neither did saline. No changes in blood pressure or heart rate were induced by any of the blockades. 4. Whereas beta-adrenoceptor blockade impaired EDV, alpha-adrenoceptor blockade and neurogenic blockade caused a general vasodilation that was not endothelium dependent. Neuropeptide Y does not seem to influence blood flow in the resting forearm.
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| 2. |
- von zur Mühlen, Bengt, et al.
(författare)
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Ambulatory blood pressure and endothelium-dependent vasodilation in hypertensive patients
- 2000
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Ingår i: Blood Pressure. - : Informa UK Limited. - 0803-7051 .- 1651-1999. ; 9:2-3, s. 110-115
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Tidskriftsartikel (refereegranskat)abstract
- Endothelial function is important for local vascular regulation and an abnormal endothelium-dependent vasodilatation (EDV) has been observed in subjects with essential hypertension. As ambulatory blood pressure (ABP) is more closely related to target organ damage than office blood pressure, this study investigated also if 24-h ABP is more closely related to an impaired EDV than office blood pressure recordings. In a group of 25 untreated patients with essential hypertension and an age- and sex-matched control group (n = 21) endothelial function was evaluated by measurements of forearm blood flow (FBF) during local intra-arterial infusions of metacholine (evaluating EDV) and sodium nitroprusside (evaluating endothelium independent vasodilation, EIDV). FBF was measured with venous occlusion plethysmography. Both office mean artery pressure (MAP; r= -0.57, p < 0.001) and 24-h ABP (r = 0.40, p < 0.01) were related to the endothelial vasodilator function (EDV to EIDV ratio) in an inverse way, but ABP was not superior to office blood pressure recordings. Within the hypertensive group, pronounced white-coat effect (office minus daytime ABP) was associated with a reduced,EDV (r= 0.41, p < 0.05). The degree of night-time decline in blood pressure ("dipping") showed no correlation to EDV. In conclusion, the finding that ABP was no more closely related to the endothelial vasodilator function than office blood pressure recordings might be due to an increased mental alertness affecting EDV in some hypertensive subjects, as suggested by the finding of a reduced EDV in those with a pronounced white-coat effect.
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| 3. |
- von zur Mühlen, Bengt
(författare)
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Antihypertensive treatment and endothelial vasodilatory function
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The endothelium integrates vascular tone by the synthesis of vasoactive substances secreted abluminally to the underlying vascular smooth muscle. Endothelial function has previously been shown to be impaired in primary, secondary and experimental forms of hypertension. In this thesis the influence of antihypertensive drugs on endothelium-dependent vasodilation (EDV) was evaluated in the in vivo circulation of the human forearm. Ambulatory blood pressure (ABP) was not found to be more closely related to endothelial vasodilatory function than office blood pressure. Within the hypertensive group, there was a relationship between the white-coat effect and EDV. Local infusion of principally different beta-blocking agents induced divergent effects on EDV. In normotensive subjects propranolol impaired EDV, atenolol showed a tendency to improve EDV and labetalol enhanced both EDV and endothelium-independent vasodilation (EIDV). Drugs commonly used in the treatment of hypertension and congestive heart failure were also evaluated by local infusions in normotensive subjects. Without lowering blood pressure, enalaprilat and furosemide improved EDV, whereas no major effects were induced by digoxin or metoprolol. Furthermore, locally given captopril and systemically administered enalaprilat acutely improved EDV in patients with untreated hypertension and in normotensive subjects. After 3 months of randomized, double-blind treatment with the angiotensin II subtype-1(AT1) receptor antagonist irbesartan, or the β1-selective adrenoreceptor antagonist atenolol improved EDV. In conclusion, antihypertensive drugs were found to have a divergent influence on endothelial vasodilatory function in acute studies, whereas antihypertensive treatment for 3 months improved EDV in a randomized double-blind trial.
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| 4. |
- von zur Mühlen, Bengt, et al.
(författare)
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Divergent effects of different beta-blocking agents onendothelium-dependent vasodilatation in the human forearm
- 2000
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Ingår i: Blood Pressure. - : Informa UK Limited. - 0803-7051 .- 1651-1999. ; 9:5, s. 287-292
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of this study was to evaluate the direct effect of three principally different beta-receptor blocking agents on endothelium-dependent vasodilatation (EDV) in the human forearm. METHODS: In 27 young normotensive subjects forearm blood flow (FBF) was measured with venous occlusion plethysmography during local intra-arterial infusions of methacholine (MCh), evaluating EDV, and sodium nitroprusside (SNP), evaluating endothelium-independent vasodilatation (EIDV). The measurements of EDV and EIDV were undertaken at baseline conditions and repeated after 1 h of concomitant intra-arterial infusion of atenolol (n = 8, 1.2 mg/h), propranolol (n = 7, 1.2 mg/h), labetalol (n = 7, 16 mg/h) or saline (n = 5). RESULTS: The selective beta-blocker atenolol showed a tendency to improve the FBF response to MCh (from 28.8 +/- 9.2 to 32.6 +/- 8.7 ml/min/ml tissue, p < 0.05). The nonselective beta-blocker propranolol attenuated the FBF response to MCh significantly (from 30.5 +/- 6.7 to 22.8 +/- 4.5 ml/min/ml tissue, p < 0.01). In these groups baseline FBF and EIDV were unchanged. Labetalol, a combined non-selective beta-blocker and selective alpha-1-blocker, increased baseline FBF and increased the response to both MCh and SNP in parallel (p < 0.05 for MCh and p = 0.07 for SNP). Saline did not change baseline FBF, EDV or EIDV. CONCLUSIONS: This study showed that local infusion of different beta-blocking agents in normotensive subjects affects endothelial vasodilatory function differently. This technique could be used to evaluate the direct effect of vasoactive drugs on EDV.
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| 5. |
- von zur Mühlen, Bengt, et al.
(författare)
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Effects of digoxin, furosemide, enalaprilat and metoprolol on endothelial function in young normotensive subjects
- 2001
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Ingår i: Clinical and experimental pharmacology & physiology. - : Wiley. - 0305-1870 .- 1440-1681. ; 28:5-6, s. 381-385
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- 1. Endothelial dysfunction is seen in patients with essential hypertension or congestive heart failure (CHF). The present study aimed to evaluate the direct effect on endothelium- dependent vasodilation (EDV) of different pharmacological drugs commonly used in the treatment of these conditions. 2. Forearm blood flow (FBF) was measured in 37 young healthy normotensive subjects with venous occlusion plethysmography during local intra-arterial infusions of methacholine (MCh; 2-4 microg/min), evaluating EDV, and sodium nitroprusside (SNP; 5-10 microg/min), evaluating endothelium-independent vasodilation (EIDV). The measurements of EDV and EIDV were undertaken under baseline conditions and were repeated after 1 h intra-arterial infusion of digoxin (0.1 mg/h), furosemide (5.0 mg/h), enalaprilat (2,4 mg/h), metoprolol (1.2 mg/h) or saline (controls). 3. Enalaprilat and digoxin improved the FBF response to MCh at 4 microg/min (from 22.7+/-2.3 to 25.5+/-2.1 mL/min per 100 mL tissue (P < 0.01) and from 18.2+/-2.4 to 22.2+/-2.0 mL/min per 100 mL tissue (P < 0.05), respectively). No significant changes where induced by furosemide or metoprolol in response to MCh at 4 microg/min (from 19.4+/-2.0 to 22.9+/-2.8 and from 15.3+/-2.4 to 14.7+/-1.1 mL/min per 100 mL tissue, respectively). No significant changes in basal FBF or EIDV were induced by the different drugs. When the endothelial function index was calculated as the MCh: SNP FBF ratio, a significant improvement was seen only with enalaprilat (1.1+/-0.1 to 1.2+/-0.1; P < 0.01) and furosemide (1.0+/-0.1 to 1.3+/-0.4; P < 0.05). 4. In conlusion, the results of the present study show that enalaprilat and furosemide improve endothelial vasodilatory function, while no major effect was induced by digoxin or metoprolol. Thus, different direct effects on the endothelium in young normotensive subjects were induced by drugs commonly used in the treatment of hypertension or CHF.
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| 6. |
- von zur Mühlen, Bengt, et al.
(författare)
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Treatment with irbesartan or atenolol improves endothelial function in essential hypertension
- 2001
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Ingår i: Journal of Hypertension. - : Ovid Technologies (Wolters Kluwer Health). - 0263-6352 .- 1473-5598. ; 19:10, s. 1813-1818
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- OBJECTIVES: To investigate if antihypertensive treatment could improve endothelium-dependent vasodilatation in hypertensive patients, and whether the angiotensin II subtype-1 (AT1)-receptor antagonist irbesartan and the beta1-receptor antagonist atenolol would differ in this respect. SUBJECTS AND METHODS: Thirty-four patients (28 men and six women) with mild-to-moderate essential hypertension (diastolic blood pressure 90-120 mmHg) were randomized to once daily 150-300 mg irbesartan or 50-100 mg atenolol in a double-blind fashion, preceded by a placebo run-in period. Forearm blood flow (FBF) was assessed by venous occlusion plethysmography during local intra-arterial infusions of methacholine and sodium nitroprusside, to evaluate endothelium-dependent and endothelium-independent vasodilatation, respectively. Measurements of FBF were undertaken at the end of the run-in placebo period and repeated after 3 months of active antihypertensive treatment. RESULTS: Irbesartan and atenolol induced a similar decline in blood pressure (from 171/107 to 158/98 mmHg, P < 0.05), and improved endothelium-dependent vasodilatation (e.g. an increase in FBF response to 4 microg/min methacholine from 325 +/- 29% to 411 +/- 41%, P < 0.05), with no difference between the two study drugs. No significant changes in endothelium-independent vasodilatation were induced by irbesartan or by atenolol. CONCLUSIONS: The present study shows that 3 months of antihypertensive therapy with irbesartan or atenolol improves endothelium-dependent vasodilatation.
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