Triple papillary fibroelastomas in an asymptomatic patient.

Papillary fibroelastoma is the third most common type of primary cardiac tumour. Even though the majority of patients with these tumours are asymptomatic, they may present with embolic phenomena, syncope and death. This report describes a patient with papillary fibroelastomas affecting all three cusps of the aortic valve, with accompanying transoesophageal echocardiography and images of surgical specimens of the tumours.

Assessment of the stability of pesticides during cryogenic sample processing. 1. Apples.

An assessment of the stability of a large number (106) of pesticides and related compounds during the cryogenic sample processing of apples has been undertaken. For the first time the procedure included an assessment of the losses during the freezing of the fruits, prior to processing. The stability of each pesticide during processing was assessed by comparing the mean recovery for the laboratory-spiked samples with the mean "survival" of the pesticides in cryogenically processed samples. The results clearly demonstrate that the vast majority, 94 of 106, of pesticides were stable during cryogenic processing. Of particular importance was that losses of several pesticides [bitertanol (95%), heptenophos (50%), isofephos (40%), and tolylfluanid (48%)] reported to occur during ambient processing of apples did not occur during cryogenic processing. Losses of dichlofluanid (54%), chlozolinate (22%), and etridiazole (40%), previously reported to occur during ambient processing of apples, were reduced to barely significant levels (10, 17, and 14%, respectively) by cryogenic processing. Small apparent losses for a few of the compounds were attributable to analytical and sample handling difficulties, rather than to losses during processing, and need further investigation.

Caffeine and stress: implications for risk, assessment, and management of hypertension.

Caffeine use is widespread, and its consumption increases during periods of stress. Caffeine raises blood pressure by elevating vascular resistance, and this effect is larger and more prolonged in hypertensive patients than in normotensive. The pressor response to caffeine occurs equally in persons at rest and under stress. The elevated baseline pressures of the hypertensive patient are therefore increased by both caffeine and stress, potentially leading to undesirably high pressures. Such combined effects on blood pressure may potentially confound the evaluation of hypertension, and possibly reduce the effectiveness of antihypertensive therapy. These effects are not abolished by pharmacologic tolerance to caffeine, as tolerance may not be complete with daily intake. The contribution of caffeine's effects to the development of hypertension warrants continued study, and caffeine use by patients merits consideration in terms of assessment and management of this disorder.

Hypertension risk status and effect of caffeine on blood pressure.

We compared the acute effects of caffeine on arterial blood pressure (BP) in 5 hypertension risk groups composed of a total of 182 men. We identified 73 men with optimal BP, 28 with normal BP, 36 with high-normal BP, and 27 with stage 1 hypertension on the basis of resting BP; in addition, we included 18 men with diagnosed hypertension from a hypertension clinic. During caffeine testing, BP was measured after 20 minutes of rest and again at 45 to 60 minutes after the oral administration of caffeine (3.3 mg/kg or a fixed dose of 250 mg for an average dose of 260 mg). Caffeine raised both systolic and diastolic BP (SBP and DBP, respectively; P<0.0001 for both) in all groups. However, an ANCOVA revealed that the strongest response to caffeine was observed among diagnosed men, followed by the stage 1 and high-normal groups and then by the normal and optimal groups (SBP F(4),(175)=5.06, P<0.0001; DBP F(4,175)=3.02, P<0.02). Indeed, diagnosed hypertensive men had a pre-to-postdrug change in BP that was >1.5 times greater than the optimal group. The potential clinical relevance of caffeine-induced BP changes is seen in the BPs that reached the hypertensive range (SBP >/=140 mm Hg or DBP >/=90 mm Hg) after caffeine. During the predrug baseline, 78% of diagnosed hypertensive men and 4% of stage 1 men were hypertensive, whereas no others were hypertensive. After caffeine ingestion, 19% of the high-normal, 15% of the stage 1, and 89% of the diagnosed hypertensive groups fell into the hypertensive range. All subjects from the optimal and normal groups remained normotensive. We conclude that hypertension risk status should take priority in future research regarding pressor effects of dietary intake of caffeine.

Gender-related effects on metoprolol pharmacokinetics and pharmacodynamics in healthy volunteers.

OBJECTIVE: To determine whether there are gender-specific differences in the pharmacokinetics and pharmacodynamics of metoprolol enantiomers. METHODS: Twenty normal volunteers (10 men and 10 women) received 100 mg oral metoprolol tartrate twice daily for a total of nine doses. Pharmacokinetics and pharmacodynamics were studied after the last dose. Subjects also completed a control pharmacodynamic study; the order of drug and control studies was randomized. Measurements of heart rate and systolic blood pressure were obtained during peak submaximal bicycle exercise testing. (R)-Metoprolol and (S)-metoprolol concentrations were determined by stereospecific HPLC. The percentage difference in exercise heart rate and systolic blood pressure (metoprolol versus control), and (R)- and (S)-metoprolol plasma concentrations were comodeled. RESULTS: Men and women showed stereoselective pharmacokinetics; (S)-metoprolol concentrations were significantly greater than those for (R)-metoprolol for both groups. Women had greater drug exposure than men (higher maximum concentration and area under the plasma concentration-time curve). No differences were observed between genders with respect to elimination half-life. Females had a greater reduction in exercise heart rate and systolic blood pressure; however, the area under the effect curve was significantly greater for heart rate only. Pharmacodynamic data were best fitted by the Hill equation with the effect site in the central compartment. The fitted maximum effect and the concentration at one-half of the maximum effect for heart rate and systolic blood pressure did not differ between men and women (P > .20). CONCLUSIONS: Gender-related differences exist in the pharmacokinetics of metoprolol enantiomers, resulting in greater drug exposure in female subjects. However, concentration-effect relationships did not differ between men and women. Therefore the observed differences in drug effects were the result of gender-specific differences in metoprolol pharmacokinetics.

Insulin-induced vasodilatation of internal carotid artery.

The increase in leg and forearm blood flow induced by insulin could be secondary to its metabolic effect on glucose uptake. We therefore investigated whether insulin causes vasodilation of the internal carotid artery, since the brain is not dependent on insulin for glucose uptake, to demonstrate that the vasodilatory effect of insulin is primary and independent of its metabolic effect. Internal carotid artery diameter was continuously monitored using a 7.5-MHz transducer linked to an Acuson XP10 ultrasonograph (Mountainview, CA) during infusion of 125 mL 10% dextrose mixed with 3 U regular insulin and 5 mmol potassium chloride over 1 hour. The internal carotid artery diameter increased progressively with time from a mean of 5.4+/-1 mm to 5.7+/-1 mm at 15 minutes, 5.9+/-1.1 mm at 30 minutes, 6+/-1.1 mm at 45 minutes, and 6.1+/-1.1 mm at 60 minutes (P < .05), an increase of 13% over baseline. Glucose was maintained between 93 and 106 mg/dL, and insulin increased from 15+/-14 microU/mL and was maintained between 34 and 47 microU/mL. There was no change in mean arterial blood pressure (MABP) or heart rate during the infusion. We conclude that insulin dilates the internal carotid artery consistently at physiological concentrations, probably independently of glucose uptake by the brain. Alterations in this effect of insulin may be of relevance in the pathogenesis of abnormalities of cerebral blood flow in type 1 and type 2 diabetics as described by our group previously.

Grapefruit juice has minimal effects on plasma concentrations of lovastatin-derived 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors.

OBJECTIVE: To evaluate the effect of regular-strength grapefruit juice, a cytochrome P4503A4 (CYP3A4) inhibitor, on the pharmacokinetics of a commonly prescribed regimen of oral lovastatin. METHODS: In a randomized crossover study, 16 healthy subjects received a single 40 mg dose of lovastatin in the evening after each consumed an 8-ounce glass of regular-strength grapefruit juice or water with breakfast for 3 consecutive days. The effect of the same grapefruit juice and water regimen on the pharmacokinetics of midazolam (2 mg oral dose given 1 hour after the third day of grapefruit juice and water) was used as a positive control in the same subjects. Plasma concentrations of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors were determined by an enzyme inhibition assay, and concentrations of lovastatin, lovastatin acid, and midazolam were determined by liquid chromatography-tandem mass spectrometry. RESULTS: The area under the plasma concentration-time profiles (AUC) and maximum plasma concentrations (Cmax) of HMG-CoA reductase inhibitors increased slightly (-30% for each) after consumption of grapefruit juice. Similar effects on AUC and Cmax (approximately 40% increase for each) were noted after analysis of samples of hydrolyzed plasma (which converts inactive lactones to active hydroxy acid species). The AUC and Cmax values for lovastatin approximately doubled in the presence of grapefruit juice, whereas the same parameters for lovastatin acid increased 1.6-fold. Grapefruit juice caused the AUC for midazolam to increase by a factor of approximately 2.4. CONCLUSIONS: Daily consumption of a glass of regular-strength grapefruit juice has a minimal effect on plasma concentrations of HMG-CoA reductase inhibitors (approximately 30% to 40% increase) after a 40 mg evening dose of lovastatin.

Estrogen improves abnormal norepinephrine-induced vasoconstriction in postmenopausal women.

OBJECTIVE: An exaggerated blood pressure response to mental stress in postmenopausal women has been reported but the underlying mechanism is not clear. In the present study, we examined the role of estrogen in the blood pressure response to mental stress. SUBJECTS AND METHODS: Hemodynamic responses to mental stress and constrictor responses to norepinephrine were compared in 18 premenopausal (mean +/- SD age 33 +/- 5 years), 22 postmenopausal women (62 +/- 7 years) and 13 postmenopausal women with estrogen replacement therapy (58 +/- 8 years). Premarin was infused in 10 postmenopausal women to determine whether estrogen attenuates norepinephrine-induced vasoconstriction. The hemodynamic responses to a standard mental arithmetic test were measured. Norepinephrine (12.5, 25, 50, 100 ng/min) was infused at 0.5 ml/min for 5 min via the dorsal hand vein. Norepinephrine (100 ng/min) combined with premarin (200 microg/min) was infused into the dorsal hand vein of postmenopausal women. Changes in venous diameter were measured by ultrasonography using a 7.5 MHz transducer. RESULTS: All study subjects were healthy, normotensive and had normal lipid profiles. The postmenopausal women showed a significantly greater blood pressure response to the mental arithmetic test than the premenopausal women or those taking estrogen replacement therapy (P < 0.01). Norepinephrine induced significant dose-dependent vasoconstriction in all three groups (P < 0.001). The postmenopausal women showed significantly greater constriction in response to norepinephrine than the premenopausal women and those taking estrogen replacement therapy (P = 0.02). Premarin significantly attenuated the norepinephrine-induced vasoconstriction in the postmenopausal women (P< 0.001). CONCLUSION: Healthy, normotensive postmenopausal women showed an exaggerated blood pressure response to mental stress. An increased vasoconstriction in response to norepinephrine and loss of estrogen-mediated vasodilation may contribute to the increased blood pressure response to stress in postmenopausal women without estrogen replacement therapy.

Vasodilatory effects of troglitazone improve blood pressure at rest and during mental stress in type 2 diabetes mellitus.

The present study examined the hemodynamic mechanisms of blood pressure (BP) lowering by troglitazone in patients with type 2 diabetes mellitus (DM) at rest and during a mental arithmetic test (MAT). Twenty-two patients with DM with normal to high-normal BP and 12 controls matched for age, gender, glucose tolerance, and BP were studied. DM subjects showed significantly higher systolic BP response during MAT than controls (157 versus 139 mm Hg; P<0.01). All 22 DM patients and 5 of 12 controls had systolic BP >140 mm Hg during MAT. Heart rate and diastolic BP were not significantly different between the 2 groups. The DM group was then randomized to receive troglitazone (n=10; 400 mg/d) or glyburide (n=12; 20 mg/d). MAT was repeated after 6 months of treatment. Both treatments reduced glucose equally (-1.7 mmol/L for troglitazone and -1.5 mmol/L for glyburide), but only troglitazone reduced insulin (-15 microU/mL; P<0.001) and C-peptide (-0.9 ng/mL; P<0.02) levels. Troglitazone significantly reduced BP at baseline (P<0.05) and systolic BP response to MAT (P<0.01), whereas glyburide did not affect BP at baseline or during MAT. Stroke volume and cardiac output did not change with either drug, but troglitazone decreased peripheral vascular resistance (-112 dyne. s. cm(-5); P<0.05). Improved insulin resistance rather than an improved glycemic control is associated with lower resting and stress BP values in patients with DM. A reduction in vascular resistance may be a primary hemodynamic mechanism of the manner in which troglitazone lowers BP. Insulin sensitizers may offer potential therapeutic advantage in subjects with DM with elevated BP.

Patterns of prescribing ACE inhibitors after myocardial infarction.

We attempted to determine physician prescribing patterns of angiotensin-converting enzyme (ACE) inhibitors in patients who experienced a myocardial infarction, stratified by left ventricular function. We retrospectively reviewed drug therapy at discharge in 534 patients to assess prescription of ACE inhibitor therapy, including dosage. Thirty-four percent of patients were discharged taking an ACE inhibitor, of whom only 11% received recommended dosages. The drugs were prescribed more often for patients who had an ejection fraction below 40% than for those with an ejection fraction of 40% or above (54% vs 28%, p<0.05). We conclude that ACE inhibitors are underprescribed for patients who experienced a myocardial infarction, illustrating the gap between clinical research and clinical practice, and the need for programs to ensure optimal medical management.

Effect of gender differences and estrogen replacement therapy on vascular reactivity.

The incidence of cardiovascular disease is lower in premenopausal women compared with men; following menopause, the risk of mortality from cardiovascular disease increases in females. Postischemic dilatation of the brachial artery has been used previously as an index of endothelium-mediated vasodilation. Using this index, we examined a group of premenopausal and postmenopausal women, some of whom were on estrogen replacement therapy (ERT). All subjects were normotensive (blood pressure [BP] <140/90 mm Hg) and normoglycemic (blood glucose, <100 mg/dL). Fourteen healthy women (mean age, 27 +/- 0.8 years; mean total cholesterol, 174 +/- 6.7 mg/dL) and fourteen healthy men (mean age, 26 +/- 1.4 years; mean total cholesterol, 181 +/- 7.2 mg/dL) were investigated. Nineteen postmenopausal women were also examined; 11 were on ERT (mean age, 55 +/- 2.1 years; mean total cholesterol, 213 +/- 6.6 mg/dL) and eight were not on ERT (mean age, 60 +/- 3.6 years; mean total cholesterol, 222 +/- 14.4 mg/dL). Ischemia was induced by inflating a cuff over the forearm to a pressure of 40 mm Hg above systolic for 5 minutes. Doppler ultrasonography (Acuson [Mountain View, CA] 128XP/10c ultrasonograph with a 7.5-MHz linear array transducer) was used to measure the brachial artery diameter before inflation and 15 seconds and 45 to 60 seconds following cuff deflation. Flow-mediated dilatation (FMD%) and hyperemia were defined as the percentage increase over basal diameter and basal flow, respectively. Postischemic median dilatation in men was 4.20% (interquartile range, 2.13% to 5.56%) and 11.48% (interquartile range, 8.70% to 14.29%) in age-matched premenopausal women (P < .01). For women on ERT, the postischemic median dilatation was 8.11% (interquartile range, 6.01% to 11.60%), as compared with 2.82% (interquartile range, 1.32% to 3.28%) for women without ERT (P < .01). Premenopausal women showed significantly greater dilatation after ischemia than postmenopausal women without ERT (P < .0001). Hyperemia was similar in all groups. These findings show that postischemic vasodilation of the brachial artery is greater in premenopausal women versus age-matched men; it is decreased in postmenopausal women, and ERT restores it toward normal. The pathophysiology underlying the diminution in postischemic dilatation may be relevant to atherogenesis and coronary artery disease (CAD).

The effects of gender on adrenergic receptor responsiveness.

This study was conducted to determine whether gender differences exist in adrenergic receptor sensitivity and baroreflex response. Adrenergic receptor sensitivity was assessed by administering sequentially increasing intravenous doses of phenylephrine and isoproterenol. Baroreflex sensitivity was determined from the slope of pulse intervals plotted against phenylephrine-induced rise in systolic blood pressure (SBP). Drug-induced changes in heart rate, blood pressure, and brachial artery diameter were measured and statistically compared. Women required a lower infusion rate of phenylephrine to increase SBP by 20 mmHg from baseline. There were no statistically significant gender-related differences in baroreflex sensitivity. The dose of isoproterenol needed to increase heart rate by 25 beats per minute from baseline also did not differ significantly between groups. Percent changes from baseline in brachial artery diameters in response to phenylephrine also were similar between groups. These data suggest that women may have greater alpha-adrenergic receptor sensitivity than men, whereas beta1-adrenergic receptor sensitivity is similar between genders. A trend toward a greater baroreflex sensitivity in men than in women was also observed. This study also provides evidence for a possible relationship between adrenergic receptor sensitivity and baroreflex sensitivity.

Hypothalamic-pituitary-adrenocortical responses to psychological stress and caffeine in men at high and low risk for hypertension.

OBJECTIVE: This study examined pituitary-adrenocortical responses to dietary doses of caffeine (3.3 mg/kg, equivalent to 2 to 3 cups of coffee), alone and combined with behavioral stress, in men at high risk versus low risk for hypertension. A randomized, double-blind, caffeine-placebo crossover design was used. METHOD: Adrenocorticotropic hormone (ACTH) and cortisol levels in plasma were assessed at rest and in response to 60-minutes of continuous work on a mental stressor (arithmetic) and a psychomotor task (reaction time) on four test sessions held on separate days. RESULTS: Tasks alone caused greater ACTH and cortisol increases in high risk men than in the low risk group. Caffeine alone elevated ACTH and cortisol in both groups, with more immediate responses in the high risk group. Both groups showed significant ACTH and cortisol responses to caffeine plus tasks, with the high risk group showing more persistent elevations. The high risk group also showed the highest levels of ACTH and cortisol after caffeine plus tasks. CONCLUSIONS: These findings demonstrate for the first time the combined effects of caffeine plus stress on ACTH and demonstrate greater corticosteroid effects in hypertension-prone men. As such, they may have implications for the dietary use of caffeine during periods of stress and in those at risk for hypertension.

Insulin-mediated venodilation is impaired in patients with high cholesterol.

Recently we have reported that insulin attenuates norepinephrine (NE)-induced vasoconstriction via a cyclic GMP-NO synthase pathway. Because hypercholesterolemia has been associated with abnormal endothelial function, we investigated whether insulin-mediated vasodilation is impaired in hypercholesterolemia. To assess vasoreactivity, NE (12.5, 25, 50, and 100 ng/min), NE (100 ng/min) combined with insulin (8, 16, 24, and 32 microU/min), and NE (100 ng/min) combined with sodium nitroprusside (0.01, 0.1, 1, 10, and 100 ng/min) were infused into dorsal hand veins. Changes in venous diameter were measured by ultrasonography, using a 7.5-MHz transducer. Twenty-two healthy, normotensive hypercholesterolemic subjects (HC; mean total cholesterol 6.93 mmol/L, HDL 1.45 mmol/L, LDL 4.81 mmol/L) and 18 age-matched normal control subjects (NC; mean total cholesterol 4.81 mmol/L, HDL 1.16 mmol/L, LDL 3.18 mmol/L) were studied. All HC had normal glucose tolerance test results. Baseline vein diameters were similar between groups, and the vasoconstrictor response to NE was not significantly different between HC and NC. Insulin significantly attenuated NE-induced vasoconstriction in NC but not in HC (P<0.01). Both groups were able to venodilate with sodium nitroprusside. To investigate the effects of cholesterol reduction on vascular reactivity, venoreactivity studies were repeated in 12 HC after treatment with 20 to 40 mg/d lovastatin for 6 weeks. There were no significant venoreactivity changes with the treatment. Plasma LDL cholesterol concentration was inversely correlated to venodilator effect of insulin (r=-0.42, P<0.02). In conclusion, insulin-mediated vasodilation is impaired in patients with high cholesterol. Absence of normal insulin-mediated but not sodium nitroprusside-induced venodilation in hypercholesterolemia suggests that insulin-mediated vasodilation is endothelium dependent.

Compliant vs non-compliant balloons. A prospective randomized study.

In this prospective randomized trial we explored the possibility of different procedural outcomes with regard to compliant (polyolefin copolymer (POC)), and non-compliant (polyethylene terapthelate (PET)) balloon materials commonly used during percutaneous transluminal coronary angioplasty (PTCA). For this purpose, 51 female and 149 male (total 200) patients were randomized to 100 compliant and 100 non-compliant balloons. Only single lesions were included in the study and patients who had PTCA for more than one lesion in different segments at different sessions were each entered separately (there were actually 49 female and 143 male patients). PTCA procedures were performed in conjunction with quantitative coronary angiographic techniques and the films were reviewed by two investigators in a blinded fashion. Statistical analysis for various procedural end-points were performed by non-paired Student t test with statistical significance being p < 0.05. There were no differences in demographic and clinical characteristics between groups. Lesion characteristics of both groups were exactly matching for vessel size, balloon size, balloon vessel ratio, minimal luminal diameter and percent stenosis of the index lesion. Similarly, minimal residual diameter, percent residual stenosis, net gain, densitometric net area gain, and maximum pressure (2.2 +/- 5 mm vs 2.1 +/- 0.6 mm, 18 +/- 17% vs 23 +/- 15%, 0.8 +/- 0.5 mm vs 0.8 +/- 0.6 mm, 48 +/- 25% vs 48 +/- 26%, 7.3 +/- 2 atm. vs 6.8 +/- 3 atm., respectively) values were not statistically different between compliant and non-compliant balloon groups. Major in-hospital complications, dissections caused by the study balloon (mostly type A and B), crossover and bail-out procedures (5 vs 3, 34 vs 32, 4 vs 3, 13 vs 14, respectively) were similar for both compliant and non-compliant balloon groups. Study balloon success rate (defined as < 50% residual stenosis or > 20% net gain in the absence of major in-hospital complications, crossovers and bail-outs) and overall procedural success rate (80% vs 74%, 90% vs 85%) were not statistically different for compliant and non-compliant balloons. In conclusion, we did not observe any statistically significant difference between compliant and non-compliant balloons in terms of immediate procedural results.

Directional coronary atherectomy versus coronary angioplasty in vessels larger than 3 mm in diameter.

It has been proposed that directional coronary atherectomy (DCA) should be an intervention of choice in larger vessels as one can achieve a greater minimal luminal diameter with DCA than with percutaneous transluminal coronary angioplasty (PTCA). This in turn should translate into a higher success rate and may even reduce the restenosis rate. The aim of this study was to compare DCA versus PTCA in vessels > 3 mm in diameter. One hundred fifty consecutive patients who met the inclusion criteria and had DCA were compared to 150 similarly selected PTCA patients. PTCA patients were selected from the era immediately preceding the advent of DCA so that selections bias could be excluded. All patients with ostial lesions, restenosis, vessels < 3 mm in diameter, and vessels with more than two significant lesions were excluded. Distal segments and circumflex cases were excluded as they formed a small subsegment. Both groups were similar in terms of demographic, clinical and angiographic variables. Quantitative analysis showed that the initial net gain was significantly greater in the DCA group than in the PTCA group (2.36 +/- 0.8 mm vs. 1.78 +/- 0.7 mm; p < 0.05). Residual stenosis was 11% with DCA compared to 33% with PTCA (p < 0.05). Despite these improved anatomical results the procedural success rates were similar (91.5% vs 84%). Major in hospital complications (death, acute occlusion, MI, emergency CABG, re-do) were higher in the DCA group than in the PTCA group (12% vs 6%). Clinical follow-up on 276 patients (150 DCA vs 126 PTCA) showed a 6 month clinical restenosis rate of 18% vs 28%, respectively. The incidence of re-do in 24 hours for acute occlusion was 6% for DCA and 1% for PTCA. In large-sized vessels DCA results in a lower restenosis rate. However, despite a lower incidence of residual stenosis, the complication rate tends to be higher with DCA (p < 0.05).

Vasoreactivity in pre- and postmenopausal women: evaluation by pharmacodynamic modeling.

Postmenopausal women experience an increase in cardiovascular mortality and morbidity compared with their premenopausal counterparts. This study was undertaken to develop a pharmacodynamic model to determine whether vascular reactivity in postmenopausal women differed from that in premenopausal women. Eleven subjects in each group were recruited. Graded doses of norepinephrine and insulin were infused via the dorsal hand vein. Venous diameter was measured by ultrasound. Dosage and venous diameter were fit to a Hill-type pharmacodynamic model in which norepinephrine acts as a vasoconstrictor and insulin counteracts varying fractions of norepinephrine constriction. Fitted pharmacodynamic parameters for norepinephrine did not differ uniformly between groups, but at norepinephrine infusion rates between 14 and 46 ng/mL, postmenopausal women demonstrated increased norepinephrine-induced vasoconstriction. Also, the modeled maximal response to insulin (Emaxi) was greater in premenopausal women. By stepwise linear regression, maximal response to insulin was found to be related to menopausal status and diastolic blood pressure. Postmenopausal women showed differences in vasoreactivity that may have important implications in the pathogenesis of hypertension.