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.

Brachial vascular reactivity in blacks.

Endothelial function was studied ultrasonographically in a healthy subset of African Americans (blacks) because they have an increased risk of hypertension and vascular disease. Twenty-four healthy black and 28 well-matched white subjects were investigated. Ischemia was induced by inflating a cuff over the forearm to 40 mm Hg higher than systolic pressure for 5 minutes. Brachial artery diameter and blood flow velocity were measured at baseline and at 15, 45, and 60 seconds after deflation by use of an Acuson 128XP10 ultrasonograph with a 7.5 MHz transducer. Mean postischemic dilatation, an index of endothelial function, was 1.76+/-0.56% in blacks and 8.79+/-1.22% in whites (P<0.001). Median postischemic vasodilatation in black men [0% (0% to 2.86%)] was not significantly different to that in black women [0.82% (0% to 3.14%)], whereas white women [11.48% (8.70% to 14.29%)] dilated significantly more than white men [4.20% (2.13% to 5.56%)] (P<0.05). Both groups dilated significantly over baseline diameter to sublingual nitroglycerin administration 18.7+/-2.5% (blacks) and 20.2+/-3.2% (whites; P=NS). Mean hyperemic responses did not differ significantly between the 2 subject groups, nor did they differ between men and women of both ethnic groups. We conclude that endothelium-dependent vasodilatation is significantly impaired in healthy, young blacks compared with whites and that gender differences are not seen in blacks with regard to this phenomenon. An impairment in endothelium-dependent NO generation may be a contributing factor to future hypertension and vascular disease in healthy blacks.

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.

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.

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.

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.

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).

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.

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.

Moderately obese, insulin-resistant women exhibit abnormal vascular reactivity to stress.

To define the hemodynamic implications of insulin resistance (IR), we compared 10 normotensive, insulin-resistant women who had abnormal glucose tolerance tests with 10 age-matched healthy normotensive women with normal glucose tolerance tests with respect to mental arithmetic and handgrip responses. Hemodynamic variables obtained at baseline and during stress included heart rate, blood pressure, cardiac output, and systemic vascular resistance. The IR group weighed more (84 versus 66 kg). Screening BP was similar (123/72 versus 120/68 mm Hg, P=NS) between groups although baseline diastolic BP at testing day was higher in the IR group than control group (75 versus 65 mm Hg, P<.05). The IR group showed a significantly greater increase in systolic (18% versus 10%, P<.O1) and diastolic (24% versus 12%, P<.01) blood pressure responses to mental stress than the control group. During mental stress, the control group demonstrated increased cardiac output (1.4 L/min) and decreased systemic vascular resistance (-120 dyne x s x cm[-5]), whereas IR subjects demonstrated increased systemic vascular resistance (119 dyne x s x cm(-5); group difference, P<.02) with only a small increase in cardiac output (0.5 L/min). Handgrip also caused a greater increase in systemic vascular resistance in the IR group (252 versus 64 dyne x s x cm(-5), P<.05), with a correspondingly greater increase in blood pressure than control subjects. Baseline blood pressure was correlated with weight (r=.41, P<.02) and stress blood pressure with fasting insulin (r=.51, P<.001) and glucose-to-insulin ratio (r= -.55, P<.001). We conclude that insulin resistance is associated with an exaggerated blood pressure response to stress; an enhanced vasoconstriction to stress may mediate this response. This hyperreactivity may be a marker for future hypertension in obese, normotensive, hyperinsulinemic individuals.

Effects of cholesterol reduction on BP response to mental stress in patients with high cholesterol.

Impaired endothelium-dependent vascular relaxation has been reported in patients with high cholesterol (HC), but the systemic effects of elevated cholesterol on blood pressure (BP) and BP reactivity to stress have not been studied. We examined the BP response to a standard mental arithmetic test (MAT) in 37 healthy, normotensive HC subjects and 33 normal cholesterol controls (NC). Both groups had similar age, body mass index, and gender distribution. HC had slightly higher systolic BP at baseline (122 v 118 mm Hg, P < .05) than NC and systolic BP response during MAT was significantly higher in HC compared to NC (18 +/- 8 v 10 +/- 5 mm Hg, P < .05). Maximal changes in systolic BP were significantly correlated with cholesterol (R = 0.41, P < .001), whereas heart rate and diastolic BP changes were unrelated to serum cholesterol. To confirm that BP reactivity was dependent on cholesterol, MAT was repeated after treatment with 20 mg/day of lovastatin, a hepatic hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitor, for 6 weeks using a cross-over design in 26 HC subjects. Lovastatin significantly altered lipid profiles (-26% total cholesterol, +8% HDL, -34% LDL). A small decrease in systolic BP at baseline (-3 mm Hg, P = NS) and significantly lower systolic BP (-8 mm Hg, P < .05) during MAT was observed after the treatment with lovastatin. In conclusion, patients with high cholesterol had an exaggerated systolic BP response to MAT. Decreased BP reactivity during HMG-CoA reductase inhibitor therapy suggests that lowering cholesterol may have a role in the overall control of BP.

Acute blood pressure elevations with caffeine in men with borderline systemic hypertension.

Whether the vasoconstrictive actions of caffeine are enhanced in hypertensive persons has not been demonstrated. Thus, caffeine (3.3 mg/kg) versus placebo was tested in 48 healthy men (aged 20 to 35 years) selected after screening on 2 separate occasions. Borderline hypertensive men (n = 24) were selected with screening systolic blood pressure (BP) of 140 to 160 mm Hg and/or diastolic BP 90 to 99 mm Hg. Low-risk controls (n = 24) reported no parental history of hypertension and had screening BP < 130/85 mm Hg. Participants were then tested on 2 occasions after 12-hour abstinence from caffeine in each of 2 protocols; this required a total of 4 laboratory visits. Caffeine-induced changes in diastolic BP were 2 to 3 times larger in borderline subjects than in controls (+8.4 vs +3.8 mm Hg, p < 0.0001), and were attributable to larger changes in impedance-derived measures of systemic vascular resistance (+135 vs +45 dynes.s.cm-5, p < 0.004). These findings were consistent and reached significance in both protocols. The percentage of borderline subjects in whom diastolic BP changes exceeded the median control response was 96%. Consequently, whereas all participants exhibited normotensive levels during the resting predrug baseline, 33% of borderline subjects achieved hypertensive BP levels after caffeine ingestion. Thus, in borderline hypertensive men, exaggerated responses to caffeine were: selective for diastolic BP, consistent with greater vasoconstriction, replicated in 2 protocols, and representative of nearly all borderline hypertensives. We suspect that the potential for caffeine to stabilize high resistance states in susceptible persons suggests that its use may facilitate their disease progression, as well as hinder accurate diagnosis and treatment.

Caffeine and behavioral stress effects on blood pressure in borderline hypertensive Caucasian men.

Caffeine in dietary amounts raises blood pressure (BP), and its use increases during work stress; however, caffeine combined with behavioral stress has not been tested in borderline hypertensive (BH) men. Accordingly, this study tested a psychomotor stressor plus caffeine (3.3 mg/kg, equivalent to 2-3 cups of coffee) using a double-blind, crossover design in 24 BH men (140/90 mmHg < or = BP < or = 160/95 mmHg) and 24 controls (BP < or = 135/85 mmHg). BH men had modestly larger BP increases to the task and showed a greater combined effect of caffeine plus the task (+15/+11 mmHg) than controls (+10/+6 mmHg). BH men maintained response to the stressor in the face of an exaggerated BP response to caffeine, suggesting that use of caffeine during behavioral stress may elevate BP in BH individuals to a clinically meaningful degree.

Caffeine elevates blood pressure response to exercise in mild hypertensive men.

The present study examined the effects of caffeine on blood pressure (BP) regulation in hypertensive men during exercise. Twenty unmedicated, mild hypertensives (HT, BP = 140/90 to 160/105 mm Hg) and 12 age-matched, normotensives (NT, BP < 130/80 mm Hg) performed 30 min of extended bicycle exercise following a single dose of caffeine (3.3 mg/kg, equivalent to 2 to 3 cups of coffee) and placebo in a double-blind, cross-over design. Hemodynamic measurements were made at predrug, 40-min postdrug and during exercise. At predrug baseline, HT had significantly higher HR (67 v 57 beats/min) and BP (141/96 v 118/72 mm Hg) than NT. At postdrug baseline, caffeine increased systolic and diastolic BP, and peripheral vascular resistance (P < .01 in all cases), decreased HR (P < .05) and did not significantly change stroke volume and cardiac output for both groups. During exercise, HR response was greater on caffeine day than placebo day in HT (P < 0.05) only. Systolic BP was consistently elevated on caffeine day compared to placebo day in both groups (P < .001). Diastolic BP was elevated in HT for 30 min of exercise on caffeine day, but this pressor effect disappeared at 15 min of exercise in NT. As a result, rate-pressure products were significantly higher on caffeine days in HT at postdrug and during exercise. On caffeine day, 7 (39%) HT and 1 (8%) NT showed an excessive BP response (> 230 for systolic or > 120 for diastolic) during exercise. In conclusion, caffeine has significant hemodynamic effects on mild hypertensives at rest and during exercise. The increased rate-pressure products following caffeine during exercise place a greater workload on the heart, and abstinence from caffeine, especially before exercise, may be beneficial for persons with hypertension.

Insulin attenuates norepinephrine-induced venoconstriction. An ultrasonographic study.

To directly assess insulin-related venomotor changes objectively and quantitatively, we used a modified ultrasonographic technique to measure venous diameter. Ten healthy men and women were studied by use of an Acuson 128 XP ultrasonograph with a linear 7.5-MHz ultrasonographic transducer (sensitivity, +/- 0.1 mm). Venous diameter was measured with the arm kept at 30 degrees elevation and with a pneumatic cuff above the elbow inflated at 40 mm Hg for the last 2 minutes of each 5-minute observation period. Norepinephrine was infused at incremental concentrations of 12.5, 25, 50, and 100 ng/min (75, 150, 300, and 600 pmol/min, respectively) for 5 minutes each. Maximal venoconstriction was achieved by the dose of 100 ng/min norepinephrine, which was then combined with insulin doses of 8, 16, 24, and 32 microU/min (60, 120, 180, and 230 fmol/min, respectively) for 5 minutes each. In six different subjects, methylene blue, an inhibitor of guanylate cyclase, was infused simultaneously with 32 microU/min insulin and 100 ng/min norepinephrine. Mean resting diameter of the vein (1.8 +/- 0.6 mm [mean +/- SD]) increased (to 3.0 +/- 1.0 mm) after cuff inflation. Incremental doses of norepinephrine caused highly reproducible dose-dependent decrease in venous diameter (to 1.8 +/- 0.6 mm, P < .001). Incremental doses of insulin, when combined with the maximum dose of norepinephrine, caused highly reproducible dose-dependent increases in mean venous diameter (P < .001) compared with norepinephrine alone. Methylene blue, which had no independent effect on venous diameter, inhibited the venodilator effect of insulin (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocortical effects of caffeine at rest and during mental stress in borderline hypertensive men.

We examined the effect or dietary doses of caffeine (3.3 mg/kg, equivalent to 2 to 3 cups of coffee) on adrenocortical responses to behavioral stress in borderline hypertensive (BH) men using a randomized, double-blind, caffeine-placebo crossover design. Cortisol levels were assessed in BH men and matched normotensive (NT) controls at rest and in response to 35 min of continuous work on a psychomotor task alternating with mental arithmetic. Caffeine at rest elevated cortisol among BHs hut not among NTs. Both groups showed significant cortisol responses to caffeine combined with the tasks. These findings may have implications for the dietary use of caffeine in persons at risk for hypertension when faced with stressful situations.

Prolonged increase in blood pressure by a single oral dose of caffeine in mildly hypertensive men.

Caffeine is known to raise blood pressure (BP). We examined a single oral dose of caffeine (3.3 mg/kg, equivalent to 2 to 3 cups of coffee) on BP in 18 hypertensive (HTN) and 12 age-matched, normotensive (NT) men for 3 h. Systolic BPs were significantly higher after caffeine for both groups (P < .001) for the entire 3 h. The HTN group showed persistent elevation in diastolic BP for 3 h, whereas the increment of diastolic BP became smaller in the NT group 90 min after caffeine ingestion. Our results suggest that caffeine consumption may affect both diagnosis and treatment of hypertension and abstinence from caffeine may be beneficial, especially for hypertensive individuals.

Cardiac adaptation to increased systemic blood pressure in borderline hypertensive men.

The present study examined cardiac characteristics of borderline hypertensive men with a positive parental history of hypertension. Hemodynamics in relation to left ventricular function and structure were evaluated in 15 borderline hypertensive men with a parental history of hypertension and in 20 normotensive control subjects with a negative parental history. Groups were matched in age, height, weight and percent body fat. Left ventricular mass and dimensions were measured by M-mode echocardiography, and left ventricular function was assessed by radionuclide ventriculography. Both groups had similar left ventricular mass, dimensions and wall thicknesses. In relation to control subjects, borderline hypertensive men had a significantly higher heart rate and blood pressure (BP) (p < 0.001), but a similar cardiac index. Borderline hypertensive men had a higher peripheral resistance index (p < 0.02), longer time to peak filling rate, and reduced cardiac efficiency, whereas they had higher contractility, minute and stroke work indexes than did control subjects (all p < 0.05); they also had higher diastolic BP (p < 0.03) during exercise, and sustained higher BP during recovery than did controls. Although this group of borderline hypertensive men did not have an altered cardiac anatomy, they had an increased vascular resistance, an altered diastolic function and a reduced cardiac efficiency while undergoing a greater work load. These cardiodynamic profiles are consistent with functional vascular changes and a parallel compensation by the heart.(ABSTRACT TRUNCATED AT 250 WORDS)

Consistency of cardiovascular response pattern to caffeine across multiple studies using impedance and nuclear cardiography.

This paper illustrates the use of impedance cardiography in an applied research setting to examine some of the pharmacological effects of caffeine on cardiovascular function. A primary advantage of the technique was in providing a noninvasive approach for studying cardiac versus vascular mechanisms underlying blood pressure responses to acute caffeine challenge. Impedance cardiography allowed the quantification of stroke volumes and cardiac output, and the change in these variables over time in a within-subjects design. Systemic vascular resistances were then calculated when impedance data were combined with simultaneously measured blood pressures. Results from four studies are summarized in which caffeine significantly elevated systolic and diastolic blood pressures. Impedance-derived measures indicate that caffeine's pressor response can be attributed to increased systemic vascular resistance rather than to elevated cardiac output. Our findings were consistent across all four studies, and across all protocols within those studies. Furthermore, these response patterns were confirmed by obtaining similar results using nuclear ventriculography. Thus, with respect to the outcome of testing an applied question, impedance-derived findings were found to be reliable and valid when compared with another technique used more commonly in clinical settings.