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The forearm vascular response to nitric oxide (NO) and calcitonin gene-related peptide (CGRP) was investigated in 10 migraine patients and 10 matched control subjects. Changes in forearm blood flow (FBF) during intrabrachial infusion of: (i) serotonin (releasing endogenous NO), (ii) sodium nitroprusside (SNP, exogenous NO-donor), and (iii) CGRP were measured using venous occlusion plethysmography. Flow-mediated dilation (FMD) of the brachial artery, a measure for the endogenous release of NO reactive to occlusion, was measured using ultrasound and expressed as percentage change vs. baseline diameter. FBF ratio (i.e. FBF in the infused over the control arm) at baseline (1.1 ± 0.1) did not differ between both populations. Serotonin, SNP and CGRP induced a dose-dependent increase ( P < 0.001) in FBF ratio in controls (to 2.8 ± 0.3, 6.7 ± 1.4 and 6.9 ± 1.2 at the highest dose, respectively) and migraineurs (2.5 ± 0.4, 5.6 ± 0.8 and 6.5 ± 1.3, respectively); these ratios did not differ between both groups. FMD was comparable in control subjects (5.8 ± 1%) and migraine patients (5.2 ± 1%). Based on the forearm vascular response to NO and CGRP, migraine patients do not display generalized changes in vascular function. [ABSTRACT FROM AUTHOR]

Type I diabetic patients (DM-1) with an elevated urinary albumin excretion (UAE>30?mg/24?h) have a high cardiovascular risk. However, DM-1 patients with normal UAE have incipient abnormalities of the cardiovascular and nervous systems, such as elevations of blood pressures, increases in arterial stiffness and deterioration of autonomic nervous function. We studied the interrelationships of these abnormalities in normoalbuminuric DM-1 patients. In 76 patients, we performed two cardiovascular reflex tests (deep in- and expiration test (IE test) and lying-to-standing test (LS test)), and determined aortic pulse wave velocity (PWV), local arterial compliances of the common carotid, femoral and brachial arteries, and 24-h blood pressures. The?RRmax value of the LS test was associated with aortic PWV (negatively) and the compliance coefficients of the carotid, femoral and brachial arteries. Per 100-ms increase in?RRmax, pulse wave velocity decreased by 0.39?m/s, compliance coefficients of the carotid, femoral and brachial arteries increased by 0.06, 0.08 and 0.05?mm2/kPa, respectively. These associations were independent of age, 24-h mean arterial pressure and 24-h heart rate. Increases in arterial stiffness were associated with increases in 24-h systolic and pulse pressure (per 1?m/s increase in PWV, systolic and pulse pressure increased by 2.1 and 1.7?mmHg, respectively). In normoalbuminuric DM-1 patients, deterioration of autonomic nervous function is associated with an increase in arterial stiffness, which, in turn, was associated with, and may cause, increased systolic and pulse pressure. These findings suggest that preventive strategies targeting autonomic dysfunction may reduce cardiovascular morbidity in diabetes.Journal of Human Hypertension (2004) 18, 761-768. doi:10.1038/sj.jhh.1001751 Published online 3 June 2004 [ABSTRACT FROM AUTHOR]

Aims To investigate the peripheral vascular effects and pharmacokinetics of dihydroergotamine (DHE) 0.5 mg after a single subcutaneous administration in humans. Methods A double-blind, placebo-controlled cross-over study was performed in 10 healthy male subjects. A wash-out period of 2 weeks separated the two study periods. During each period, just before and at regular intervals after drug administration, vascular measurements were performed and venous blood samples were drawn. Vessel wall properties were assessed at the brachial artery, by ultrasound and applanation tonometry. Blood pressure and heart rate were recorded with an oscillometric device. Forearm blood flow was measured with venous occlusion plethysmography. For all parameter-time curves the area under the curve (AUC) was calculated. Differences in AUC after placebo and DHE (ΔAUC) were analysed and the time-course of the difference assessed. DHE pharmacokinetics were analysed according to a two-compartment open model with an absorption phase. Results AUC for blood pressure, heart rate and forearm vascular resistance did not change after DHE. Brachial artery diameter and compliance decreased (P < 0.01); ΔAUC (95% confidence interval) equalled -8.81 mm h (-12.97/-4.65) and -0.98 mm2 kPa-1 h (-1.61/-0.34), respectively. Diameter decreased (P < 0.05) from 1 until 24 h after DHE (peak decrease 9.7% at 10 h); compliance from 2 until 32 h (24.8% at 2 h). Time to reach maximum plasma concentration of DHE averaged 0.33 ± 0.08 h (± s.e.mean); terminal half-life was 5.63 ± 1.15 h. Conclusions DHE decreased diameter and compliance of the brachial artery whereas forearm vascular resistance remained unchanged. Thus, DHE acts on conduit arteries without affecting resistance arteries. Furthermore, a discrepancy was demonstrated between the plasma concentrations of DHE which rapidly reach peak levels and quickly decline, and its long lasting vasoconstrictor activity. [ABSTRACT FROM AUTHOR]

Objectives: To compare quality of life with the selective β[SUB1]-blocker bisoprolol and the thiazide diuretic bendrofluazide in patients with mild to moderate hypertension. Design and setting: Multi centric, randomised, double-blind, two-way crossover study carried out at six general practice centres. Subjects: Eighty-one patients with newly diagnosed or previously treated hypertension, who had a mean diastolic blood pressure (BP) of 95-120 mm Hg after receiving placebo for 4-6 weeks. Interventions: In random order, patients received bisoprolol (5 mg once daily) or bendrofluazide (2.5 mg once daily) for 8 weeks. Main outcome measures: Quality of life and antihypertensive effect. Results: Decrease in systolic/diastolic BP did not differ between bisoprolol (10 ± 2/13 ± 1 mm Hg) and bendrofluazide (9 ± 2/11 ± 1 mm Hg). Between bisoprolol and bendrofluazide neither in the intention-to-treat nor in the efficacy analysis any difference was found in quality of life variables, such as Health Status Index, somatic symptoms, anxiety, depression, total psychiatric morbidity, cognitive symptoms and hostility score. Compared to baseline the Health Status Index improved (P < 0.05) during bisoprolol. None of the other investigated quality of life variables changed compared to baseline. No patients dropped out during bisoprolol or bendrofluazide treatment. Although, the total number of reported adverse events appeared lower during bendrofluazide than during bisoprolol treatment, it is unclear whether drug related adverse events also differ between the two drugs. Conclusions: At equipotent antihypertensive dosages, the effect of an 8-week treatment on quality of life does not differ between the selective β[SUB1]-blocker bisoprolol and the thiazide diuretic bendrofluazide. [ABSTRACT FROM AUTHOR]

Nitrates decrease pulse pressure more than mean arterial pressure (MAP) and are advocated for the treatment of isolated systolic hypertension (ISH). Nitrates show drug tolerance during chronic treatment so an asymmetric dosing regimen may prevent loss of effect of nitrates. This study investigates the anti-hypertensive effect of isosorbide dinitrate (ISDN) given in a twice daily asymmetric dosing regimen in elderly patients with ISH. After a 6-week placebo run-in period, patients entered the double-blind study. Ten patients received placebo and 11 patients ISDN 20 mg b.i.d. for 8 weeks. This dose could be doubled once. Office systolic and diastolic blood pressures (SBP/DBP) and ambulatory BP were measured. Pulse pressure was calculated as SBP-DBP. Office pulse pressure was more reduced during ISDN (17.9%) than with placebo (5%; P < 0.05). SBP and MAP decreased compared to baseline, but the changes were not statistically significant between the two groups. DBP tended to increase with ISDN compared to placebo. Mean 24-h, mean daytime and mean night-time pulse pressure decreased after treatment with ISDN (10.7%, 12.1%, 7.9%, respectively). Pulse pressure tended to decrease more during the day than during the night with ISDN. No changes could be demonstrated with placebo. In conclusion, pulse pressure decreased with ISDN, resulting in a lower SBP without a decrease in DBP. The latter may preserve coronary perfusion in ISH. With the asymmetric dosing regimen the decrease in pulse pressure was not clear at night. Whether a decrease in nocturnal BP, in addition to the spontaneous decrease, is advisable in ISH remains a matter of debate. [ABSTRACT FROM AUTHOR]