The present study, involving 56 healthy subjects from a health screening, was undertaken to address some methodological questions regarding the measurement of endothelial function using local intra-arterial infusions of metacholine (2 and 5 micrograms min-1) to evaluate endothelium-dependent vasodilatation, and sodium nitroprusside (SNP, 5 and 10 micrograms min-1) to evaluate endothelium-independent vasodilatation. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. The ratio of FBF during the highest dose of metacholine to FBF during the highest dose of SNP was used as an index of endothelial function. In 10 young volunteers the procedure was repeated after 2 h and again after 3 weeks in order to study short-term and long-term reproducibility of the method. Neither the vasodilatatory response to metacholine (r = 0.006) nor that to SNP (r = 0.08) was related to resting FBF. Neither the circumference nor the length of the arm was related to endothelial function (r = 0.01-0.11), as evaluated by the FBF on metacholine to nitroprusside ratio (mean 1.3 +/- 0.3 SD). The use of a wrist cuff to exclude hand circulation, or not, did not influence the evaluation of endothelial function significantly. Maximal FBF after 3 min of arterial occlusion of the forearm was significantly related to blood flow during both metacholine (r = 0.53, P < 0.01) and nitroprusside infusion (r = 0.36, P < 0.05), but not to the FBF on metacholine to nitroprusside ratio (r = 0.01). The short-term and long-term reproducibility of FBF during vasodilatation with metacholine and SNP was good (r = 0.89-0.97, P < 0.001), while the individual measurements for resting FBF were less reproducible when repeated after 3 weeks (r = 0.34). In conclusion, endothelial function was not related to resting FBF, nor to the arm circumference or length. No major difference was seen whether endothelial function was evaluated with or without exclusion of the hand circulation. Maximal FBF during reactive hyperaemia was not related to endothelial function.

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Abstract. Sarabi M, Millga Êrd J, Lind L (University Hospital, Uppsala, Sweden). Effects of age, gender and metabolic factors on endothelium-dependent vasodilation: a population-based study. J Intern Med 1999; 246: 265±274.Objectives. A progressive decline in endotheliumdependent vasodilation (EDV) in the human forearm with age has previously been reported. The aim of this study was to evaluate the interplay between age, gender and metabolic factors on EDV in healthy subjects in a population-based study. Setting. Tertiary university hospital. Subjects and design. Thirty-six healthy men and 30 women, aged 20±69 years, underwent measurements of forearm blood flow (FBF) at rest and during local infusions of 2 and 4 mg min 21 of metacholine (evaluating EDV) and 5 and 10 mg min 21 of sodium nitroprusside (evaluating endothelium-independent vasodilation, EIDV) and during reactive hyperaemia by venous occlusion plethysmography. Results. Age was inversely related to EDV (r = ± 0.41, P , 0.05 in men; r = ± 0.61, P , 0.01 in women) and maximal FBF during reactive hyperaemia in both men and women. EIDV was significantly related to age in an inverse way in women only. EDV was more pronounced in females than in males before menopause (48 6 3 SD years, 635 6 186 vs. 502 6 269% in males, P , 0.05), but similar in women and men thereafter (374 6 141 vs. 370 6 185% in men). The slope of the regression line for the relationship between age and EDV was flatter in premenopausal than in postmenopausal women (± 2.3 vs. ± 6.4), whilst this slope was similar in younger and older men (± 5.5 vs. ± 5.3). In multiple regression analysis, fasting blood glucose levels and the waist/hip ratio remained the only significant predictors of EDV in men (P , 0.01 for both), whilst age was the only significant independent predictor of EDV in women (P , 0.01). Conclusion. The interplay between age and metabolic factors as determinants of endothelial function is different in healthy men and women.

The present study aimed to investigate the influence of the angiotensin-converting enzyme (ACE)-inhibitor captopril and the Ca-antagonist nifedipine on endotheliumdependent vasodilation (EDV) in the forearm of hypertensive patients. Twenty-three middle-aged untreated hypertensive patients underwent evaluation of EDV and endothelium-independent vasodilation (EIDV) in the forearm, by means of local intra-arterial infusions of methacholine (MCh, evaluating EDV) and sodiumnitroprusside (SNP, evaluating EIDV), before and 1 h after intake of either captopril (25 mg) or nifedipine (10 mg) in a randomised, double-blind fashion. A matched normotensive control group was investigated at baseline conditions only. Five of the hypertensives were also evaluated after 3 months of treatment with captopril 25 mg twice daily in an open pilot study.First, the vasodilation induced by methacholine (MCh), but not SNP, was significantly attenuated in the hypertensive patients compared to the normotensive controls (P Ͻ 0.001 at MCh 4 g/min).Second, although the two drugs induced a similar