Michael F. Wilson

Exaggerated pressure response to exercise in men at risk for systemic hypertension

Normotensive persons at high risk of developing systemic hypertension have greater cardiovascular reactivity to mental and physical stressors. This study compared cardiovascular responses to exercise in normotensive men (aged 28 +/- 0.8 years [mean +/- standard error of the mean]) at high risk (positive parental history and high normal resting blood pressure [BP], n = 20) and at low risk (negative history, low normal BP, n = 15) of hypertension. All men had normal body weight and exercise tolerance. During graded supine bicycle exercise, 35% (7 of 20) of high-risk men had exaggerated BP responses (greater than or equal to 230/100 mm Hg) versus 0% of low-risk men, thus forming 3 groups (low risk, high-risk normal BP response, high-risk exaggerated response). Cardiac function was measured by nuclear cardiography. Cardiac index, peripheral resistance index, left ventricular ejection fraction and contractility index were measured at rest and during each exercise work load. High-risk exaggerated responders could not be distinguished from their high-risk normal-responding counterparts using resting BP or other cardiovascular variables. During exercise all 3 groups had equivalent increases in cardiac output. However, the high-risk exaggerated responders had blunting in peripheral resistance decline, resulting in excessive BP increases. This finding suggests an impaired capacity for exercise-induced vasodilation, indicating that the exaggerated response group may be at highest risk for future hypertension in these 3 groups.

Effects of caffeine on vascular resistance, cardiac output and myocardial contractility in young men☆

The mechanisms by which caffeine typically elevates blood pressure (BP) in humans have not been previously examined using a placebo-controlled design. Accordingly, oral caffeine (3.3 mg/kg body weight, equivalent to 2 to 3 cups of coffee) was given on 2 days and a placebo was given on 1 day to 15 healthy young men using a double-blind, crossover procedure. All 3 test sessions were held during a week of caffeine abstinence. Multiple measurements were made on subjects at rest (baseline values) and over a 45-minute interval after ingestion of caffeine for BP, heart rate, systolic time intervals and thoracic impedance measures of ventricular function. Baseline measurements were highly reliable for each subject across all sessions and yielded means for placebo vs caffeine days that were not different. Caffeine increased systolic and diastolic BP (p less than 0.01) and decreased heart rate (p less than 0.05). The pressor effect was due to progressively increased systemic vascular resistance and resulted in greater stroke work (p less than 0.01). There was no indication that caffeine increased cardiac output or contractility. These actions of caffeine were replicable when each caffeine day was tested separately against the placebo day. These results suggest that caffeine use by persons with cardiovascular diseases should be examined to determine whether caffeines enhancement of vascular resistance may contribute to systematic hypertension and/or create excessive demands for cardiac work.

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.

Cortisol responses to mental stress, exercise, and meals following caffeine intake in men and women

Caffeine elevates cortisol secretion, and caffeine is often consumed in conjunction with exercise or mental stress. The interactions of caffeine and stress on cortisol secretion have not been explored adequately in women. We measured cortisol levels at eight times on days when healthy men and women consumed caffeine (250 mg x 3) and underwent either mental stress or dynamic exercise protocols, followed by a midday meal, in a double blind, placebo-controlled, crossover design. Men and women had similar cortisol levels at the predrug baselines, but they responded differently to mental stress and exercise. The cortisol response to mental stress was smaller in women than in men (p=.003). Caffeine acted in concert with mental stress to further increase cortisol levels (p=.011), the effect was similar in men and women. Exercise alone did not increase cortisol, but caffeine taken before exercise elevated cortisol in both men and women (ps<.05). After a postexercise meal, the women had a larger cortisol response than the men, and this effect was greater after caffeine (p<.01). Cortisol release in response to stress and caffeine therefore appears to be a function of the type of stressor and the sex of the subject. However, repeated caffeine doses increased cortisol levels across the test day without regard to the sex of the subject or type of stressor employed (p<.00001). Caffeine may elevate cortisol by stimulating the central nervous system in men but may interact with peripheral metabolic mechanisms in women.

Gender‐related effects on metoprolol pharmacokinetics and pharmacodynamics in healthy volunteers

To determine whether there are gender‐specific differences in the pharmacokinetics and pharmacodynamics of metoprolol enantiomers.

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.

Heart rate reactivity as a predictor of neuroendocrine responses to aversive and appetitive challenges.

&NA; The present paper examines the neuroendocrine influences of aversive and reward incentives (noise and shock versus monetary bonuses) presented during reaction time tasks administered to 71 healthy men (ages 21 to 35) classified as being high (N = 30) or low (N = 41) in heart rate reactivity. High heart rate reactivity was defined as a peak heart rate increase or greater than 19 bpm to a cold pressor test administered on a different day. Independent groups of subjects worked on one of two visual reaction time tasks: either to avoid exposure to noise (115‐dBA bursts) and shock (3.5 mV, 2 sec), or to earn monetary bonuses (

Blood Pressure Response to Caffeine Shows Incomplete Tolerance After Short-Term Regular Consumption

0.50). High heart rate reactors showed significant plasma norepinephrine rises from baseline both to aversive incentives and to reward, although they showed significant cortisol responses only during aversive incentives. In contrast, the low heart rate reactors were unresponsive in cortisol and norepinephrine during either type of incentive. These results support psychoendocrine models which view the norepinephrine response as being nonspecifically related to expenditure of effort regardless of the emotional connotations of the challenge, while cortisol is seen as being secreted primarily during periods of distress. The present data further suggest that cardiovascular reactivity is linked to neuroendocrine reactivity, possibly within the central nervous system.

Brachial Vascular Reactivity in Blacks

Abstract—Caffeine acutely raises blood pressure (BP). The clinical significance of this effect depends on whether BP responses persist in persons who consume caffeine on a daily basis. Accordingly, the ability of caffeine to raise BP after 5 days of regular daily intake was tested in a randomized controlled trial. Individual differences in tolerance formation were then examined. Men (n=49) and women (n=48) completed a double-blind, crossover trial conducted over 4 weeks. During each week, subjects abstained for 5 days from dietary caffeine and instead used capsules totaling 0 mg, 300 mg, and 600 mg of caffeine per day in 3 divided doses. On day 6, in the laboratory, they used capsules with either 0 mg or 250 mg of caffeine at 9:00 am and 1:00 pm. Systolic/diastolic BP increases as a result of 250 mg of caffeine remained significant (P <0.006/0.001) at all levels of previous daily consumption. Individual difference comparisons found that although half the subjects had complete loss of systolic and diastolic BP responses to the challenge doses, the other half showed no loss in BP response, even after using 600 mg of caffeine per day for the previous 5 days (F >7.90, P <0.001). The sexes did not differ in degree of tolerance formation. Daily caffeine consumption failed to eliminate the BP response to repeated challenge doses of caffeine in half of the healthy adults who were tested. Caffeine may therefore cause persistent BP effects in persons who are regular consumers, even when daily intake is at moderately high levels.

Lack of association between free testosterone and bone density separate from age in elderly males

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.