Effect of oral contraceptives on the renin angiotensin system and renal function.

We examined the effect of oral contraceptive (OC) usage on the renin angiotensin system (RAS) in two related experiments. In the first experiment, subjects were 34 healthy, normotensive, premenopausal women, 15 OC users and 19 OC nonusers, mean age 25 +/- 1 yr, ingesting a controlled sodium diet. We assessed arterial pressure, glomerular filtration rate, effective renal plasma flow, renal vascular resistance (RVR), and filtration fraction (FF) using inulin and p-aminohippurate clearance techniques, both at baseline and in response to the ANG II receptor blocker losartan.

Comparison of two indices for forearm noradrenaline release in humans.

Although there is as yet no method which measures directly the neuronal release of noradrenaline in humans in vivo, the isotope dilution technique with [(3)H]noradrenaline has been applied to estimate forearm neuronal noradrenaline release into plasma. Two different equations have been developed for this purpose: one to estimate the spillover of noradrenaline into the venous effluent, and a modified formula (often referred to as the appearance rate) which may reflect more closely changes in the neuronal release of noradrenaline into the synaptic cleft, particularly during interventions that alter forearm blood flow. The present study was performed to compare the effects of two interventions known to exert contrasting actions on neuronal forearm noradrenaline release and forearm blood flow.

Continuous positive airway pressure improves nocturnal baroreflex sensitivity of patients with heart failure and obstructive sleep apnea.

Objectives: To determine the acute effects of continuous positive airway pressure (CPAP) on baroreceptor reflex sensitivity (BRS) for heart rate during sleep in congestive heart failure (CHF) patients with obstructive sleep apnea (OSA).

Design And Methods: In eight CHF patients with OSA not previously treated with CPAP, spontaneous BRS was assessed during overnight polysomnography prior to the onset of sleep, and during stage 2 non-rapid eye movement sleep (NREM) before, during and after application of CPAP.

Results: CPAP alleviated OSA and acutely increased the slope of BRS (median, 25%,75%) [from 3.

Reducing cardiac filling pressure lowers norepinephrine spillover in patients with chronic heart failure.

Background: We studied the cardiac sympathetic response to selective unloading of cardiopulmonary baroreceptors in subjects with normal left ventricular (LV) function and congestive heart failure (CHF).

Methods And Results: Eight patients with normal LV function (age 57+/-5 years, ejection fraction 58+/-2%) and 8 patients with CHF (age 60+/-2 years; ejection fraction 19+/-2%) were studied. Instrumentation consisted of an arterial line, a pulmonary artery catheter, and a coronary sinus thermodilution catheter.

Lack of effect of sodium nitroprusside on insulin-mediated blood flow and glucose disposal in the elderly.

Insulin increases skeletal muscle blood flow in healthy young subjects by a nitric oxide (NO)-dependent mechanism. Impairment of this mechanism may contribute to the insulin resistance of normal aging, a state characterized by reduced endothelial production of NO, an attenuated effect of insulin on skeletal muscle blood flow, and resistance to insulin-mediated glucose uptake (IMGU). We tested the hypothesis that the NO donor sodium nitroprusside (SNP) would augment insulin-mediated vasodilation and thus increase IMGU in healthy elderly subjects.

Sympathetic responses to atrial natriuretic peptide in patients with congestive heart failure.

Previous studies have shown that atrial natriuretic peptide (ANP) has relative sympathoinhibitory effects that are of potential benefit in patients with congestive heart failure (CHF). In this study, cardiac and systemic sympathetic responses to ANP were evaluated and compared with responses to sodium nitroprusside (SNP) in patients with CHF. Right- and left-heart hemodynamics were obtained simultaneously with cardiac (CANESP) and total body (TBNESP) norepinephrine spillover; these were measured by using the radiotracer technique.

1999 Canadian recommendations for the management of hypertension. Task Force for the Development of the 1999 Canadian Recommendations for the Management of Hypertension.

Objective: To provide updated, evidence-based recommendations for health care professionals on the management of hypertension in adults.

Options: For patients with hypertension, there are both lifestyle options and pharmacological therapy options that may control blood pressure. For those patients who are using pharmacological therapy, a range of antihypertensive drugs is available.

Absence of heart rate increase during inferoposterior left ventricular hypoperfusion caused by dipyridamole infusion.

Background: Stimuli such as inferoposterior myocardial infarction and right coronary injection with radiographic contrast media evoke a vasodepressor reflex characterized by bradycardia and hypotension (Bezold-Jarisch reflex). Dipyridamole acts by adenosine-mediated coronary vasodilation to disclose myocardial perfusion heterogeneity for thallium-201 scintigraphy.

Objective: To determine whether there is a relationship between the site of left ventricular hypoperfusion and the heart rate response to dipyridamole.

Effect of adenosine on heart rate variability in humans.

By stimulating afferent nerve endings in skeletal muscle, heart, kidney and the carotid body, adenosine infusion evokes a receptor-specific sympatho-excitatory reflex in humans that overrides its direct negative chronotropic effect. We tested the hypothesis that adenosine increases heart rate by suppressing parasympathetic and augmenting sympathetic components of heart rate variability. High-frequency (PH; 0.

Dissociation between microneurographic and heart rate variability estimates of sympathetic tone in normal subjects and patients with heart failure.

The concept that spectral analysis of heart rate variability (HRV) can estimate cardiac sympathetic nerve traffic in subjects with both normal and impaired left ventricular systolic function has not been validated against muscle sympathetic nerve activity (MSNA). We used coarse-graining spectral analysis to quantify the harmonic and non-harmonic, or fractal, components of HRV and to determine low-frequency (0.0-0.

Resting muscle sympathetic nerve activity and peak oxygen uptake in heart failure and normal subjects.

Aims: Exercise intolerance and increased efferent vasoconstrictor traffic to muscle are two characteristics of heart failure that have not been explicitly linked. We tested the hypothesis that peak oxygen consumption is inversely related to resting muscle sympathetic nerve activity in heart failure.

Methods And Results: We recorded peroneal muscle sympathetic nerve activity in 17 treated heart failure patients (16 men,1 woman; mean ejection fraction of 26.

Baroreflex sensitivity and the blood pressure response to beta-blockade.

The objective of this analysis was to determine whether changes in baroreflex sensitivity (BRS) within 35 hypertensive patients (25 M, 10 F, mean age 47 years) treated with beta-blockade as monotherapy relate to reductions in ambulatory blood pressure (BP) or its variability. BP was recorded intra-arterially directly from the brachial artery before and during submaximal exercise. BRS was determined by the phenylephrine injection technique.

Effect of atrial natriuretic peptide on muscle sympathetic activity and its reflex control in human heart failure.

Background: The purpose of this study was to determine if atrial natriuretic peptide (ANP) exerts a relative inhibitory effect on muscle sympathetic nerve activity (MSNA) at rest and during nonhypotensive lower body negative pressure (LBNP) in heart failure, as in healthy subjects.

Methods And Results: Fifteen men (age 39+/-2 years [mean+/-SE]) with dilated cardiomyopathy (ejection fraction 18+/-3%) received intravenous ANP (50 microgram bolus, then 50 ng. kg-1.

Baroreflex control of heart rate in a canine model of obstructive sleep apnea.

We have recently demonstrated the development of systemic hypertension in a canine model of obstructive sleep apnea (OSA), but the underlying physiological mechanisms were not identified. Therefore, the purpose of this study was to examine the effect of OSA on arterial baroreceptor control of heart rate (HR) in this canine model. OSA was produced in three dogs for 1 to 3 mo.

Entrainment of blood pressure and heart rate oscillations by periodic breathing.

Cheyne-Stokes respiration (CSR) is a form of periodic breathing associated with periodic oscillations in blood pressure (BP) and heart rate (HR), which have been attributed to hypoxia and arousals from sleep. We hypothesized that periodic alterations in ventilation alone would promote oscillations in BP and HR. Seven healthy, wakeful subjects breathed in three patterns, as follows: (1) regular breathing (RB); (2) periodic breathing with three (PB3: cycle frequency = 0.

Effects of continuous positive airway pressure on obstructive sleep apnea and left ventricular afterload in patients with heart failure.

Background: The objectives of this study were to determine the effects of continuous positive airway pressure (CPAP) on blood pressure (BP) and systolic left ventricular transmural pressure (LVPtm) during sleep in congestive heart failure (CHF) patients with obstructive sleep apnea (OSA). In CHF patients with OSA, chronic nightly CPAP treatment abolishes OSA and improves left ventricular (LV) ejection fraction. We hypothesized that one mechanism whereby CPAP improves cardiac function in CHF patients with OSA is by lowering LV afterload during sleep.

Magnitude and time course of hemodynamic responses to Mueller maneuvers in patients with congestive heart failure.

To simulate the immediate hemodynamic effect of negative intrathoracic pressure during obstructive apneas in congestive heart failure (CHF), without inducing confounding factors such as hypoxia and arousals from sleep, eight awake patients performed, at random, 15-s Mueller maneuvers (MM) at target intrathoracic pressures of -20 (MM -20) and -40 cmH2O (MM -40), confirmed by esophageal pressure, and 15-s breath holds, as apneic time controls. Compared with quiet breathing, at baseline, before these interventions, the immediate effects [first 5 cardiac cycles (SD), P values refer to MM -40 compared with breath holds] of apnea, MM -20, and MM -40 were, for left ventricular (LV) systolic transmural pressure (Ptm), 1.0 +/- 1.

Respiratory correlates of muscle sympathetic nerve activity in heart failure.

1. Sympathetic activation in congestive heart failure indicates a poor prognosis. Haemodynamic correlates of increased sympathetic nerve traffic to muscle (MSNA) and to the heart have been well characterized, but these account for only 50 to 60% of the variance in sympathetic activity between patients.

Caffeine abstinence augments the systolic blood pressure response to adenosine in humans.

Blood pressure and heart rate responses to adenosine infusion (35, 70, and 140 microg/kg/min, intravenously) were studied in 7 healthy men after 6, 30, 78, 150, and 318 hours of abstinence from regular caffeine use. The finding that caffeine abstinence augmented the systolic pressor response (from -1 +/- 2 mm Hg at 6 hours to +9 +/- 2 mm Hg at 318 hours; p = 0.01) but not the tachycardic response to adenosine has implications for current clinical and research applications of this purine.

Resting muscle sympathetic nerve activity does not predict duration of symptom-limited submaximal exercise in young patients with dilated cardiomyopathy.

Objective: To determine whether increased sympathetic vasoconstrictor drive to the calf in heart failure is associated with reduced symptom-limited submaximal exercise performance.

Design: Blood pressure, heart rate and peroneal muscle sympathetic nerve activity (MSNA) were recorded during rest and before symptom-limited treadmill exercise at 70% of resting heart rate reserve for up to 45 mins.

Patients: Thirteen young patients with dilated cardiomyopathy (age 36 +/- 2 years).

Angiotensin AT1 receptor blockade abolishes the reflex sympatho-excitatory response to adenosine.

We tested the hypothesis that endogenous angiotensin II participates in the direct and reflex effects of adenosine on the sympathetic nervous system. Nine healthy men were studied after 1 wk of the angiotensin II type I receptor antagonist losartan (100 mg daily) or placebo, according to a double-blind randomized crossover design. Bilateral forearm blood flows, NE appearance rates, and total body NE spillover were determined before and during graded brachial arterial infusion of adenosine (0.

Influence of prior exercise on stroke volume to pulse pressure ratio in young subjects with hypertension or dilated cardiomyopathy.

The objectives of this study were, first, to compare stroke volume to brachial artery pulse pressure ratios (SV/PP) as noninvasive, indirect estimates of total arterial compliance, in young subjects with primary hypertension or dilated cardiomyopathy and age-matched normal subjects and, second, to determine the influence of prior submaximal exercise on this ratio, and on calf and total peripheral vascular conductance in these subjects. We studied young patients (< 40 years old) with primary hypertension (n = 12) or dilated cardiomyopathy (n = 12) and healthy normotensive subjects (n = 12) matched for age and body size. Doppler estimated stroke volume, brachial artery pulse pressure, and calf blood flow were determined during supine rest before and 60 min after exercise.