Institute of Aerospace Medicine

Neurohumoral activation has been shown to be present in hypoxic patients with chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate whether there is sympathetic activation in COPD patients in the absence of hypoxia, and whether slow breathing impacts on sympathoexcitation and baroreflex sensitivity.

Pain sensitivity decreases with increasing resting blood pressure. This blood pressure-pain interaction may be mediated by endogenous opioids which have been shown to affect both blood pressure and nociception. To test this hypothesis, we measured mean arterial blood pressure (MAP), central venous pressure (CVP), heart rate (HR), muscle sympathetic nerve activity (MSNA), serum catecholamines, and individual pain rating scales during 2 min periods of noxious mechanostimulation (skin fold pinching) in nine young (26 +/- 2 year), male normotensive (NT) subjects and in 12 age and weight matched males with borderline hypertension (BHT). Measurements were performed before and after the i.v. administration of naloxone (0.15 mg/kg) and placebo in a randomized double-blind cross-over trial. In the pre-naloxone trials, pain led to similar changes in MAP, CVP, MSNA and plasma catecholamines in the two groups except for a higher increase in HR in the BHT group as compared to the NT group (3 +/- 1 vs. 1 +/- 1 bpm; P < 0.005). Opioid blockade with naloxone increased MSNA responses to pain in the NT group (from 5 +/- 1 to 9 +/- 1 bursts/min, and, from 100 +/- 23 to 204 +/- 36 units/min, respectively; P < 0.05) but did not significantly affect the MSNA response to pain in the BHT group. Pain induced responses of MAP, CVP, and catecholamines were not altered by naloxone in either group. Overall, there was a highly significant inverse correlation between pain perception and resting blood pressure which was not significantly affected by naloxone. The BHT subjects exhibited a lower pain perception compared to the NT subjects (P < 0.005). Naloxone increased pain rating in the NT group (from 194 +/- 9 to 218 +/- 13; P < 0.005) but not in the borderline hypertensive group (160 +/- 8 vs. 168 +/- 10; P = 0.36). Except for a decreased HR response in the BHT group, placebo had no effect on the responses to pain. Our data do not indicate a major role of the endogenous opioid system for the blood pressure-pain interaction in man. Endogenous opioids affect pain perception and sympathetic nerve activity responses to pain in normotensive men but their activity seems to be attenuated in borderline hypertensive subjects. Therefore, the lower pain sensitivity in human essential hypertension is probably mediated by non-opioid mechanisms.

Effects of angiotensin II receptor antagonism on the renal hemodynamic response to cardiovascular stress.BackgroundTo elucidate the effect of the angiotensin type 1 (AT1) receptor antagonist (AT1RA) eprosartan (E) on renal hemodynamics in normotensive and borderline hypertensive subjects, we investigated the hormonal and renal hemodynamic responses during cardiopulmonary stress testing.MethodsIn a prospective, double-blind, randomized, placebo-controlled crossover study, the effects of E

Pain sensitivity decreases with increasing resting blood pressure. This blood pressure–pain interaction may be mediated by endogenous opioids which have been shown to affect both blood pressure and nociception. To test this hypothesis, we measured mean arterial blood pressure (MAP), central venous pressure (CVP), heart rate (HR), muscle sympathetic nerve activity (MSNA), serum catecholamines, and individual pain rating scales during

Effect of erythropoietin on cardiovascular prognosis parameters in hemodialysis patients.BackgroundRenal anemia is an important determinant for left ventricular hypertrophy in dialysis patients and an independent prognosis parameter for the cardiovascular survival in dialysis patients. In addition, an autonomic dysfunction is associated with the uremic state and influences the cardiovascular risk in patients with end-stage renal disease (ESRD).MethodsWe investigated in this

Objective: Early structural and functional changes in the systemic vasculature have been proposed to play a major pathogenetic role in preeclampsia and HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. The aim of the study was to determine vascular reactivity in patients with preeclampsia with and without HELLP syndrome with respect to those in healthy pregnant control subjects.

BackgroundSelective blockade of the type 1 angiotensin II receptors (AT1 receptors) reduced blood pressure (BP) elevation caused by sympathetic stimulation in the pithed rat model. This has been attributed to blockade of AT1 receptors located presynaptically on sympathetic nerve endings normally facilitating norepinephrine release. We examined the effects of AT1 receptor blockade on the sympathetic nervous system in humans.

Background and Purpose—In 1998, 8 patients with severe, intractable arterial hypertension and MR tomography- demonstrated neurovascular contact of a looping artery at the root entry zone of cranial nerves IX and X, causing neurovascular compression, underwent neurosurgical decompression. The short-term results showed a normalization of blood pressure with a markedly reduced antihypertensive drug regimen in 7 patients. To determine the

Preeclampsia has been shown to constitute a state of sympathetic overactivity. However, it remains unclear if the sympathetic activity precedes preeclampsia or represents only a secondary phenomenon. To further investigate this issue, we performed a prospective study in pregnant women considered to be at increased risk for preeclampsia owing to preeclampsia during a preceding pregnancy. Twenty-two women with a history of preeclampsia were longitudinally studied on three occasions: twice during pregnancy (M1: 22 +/- 4, M2: 33 +/- 5 weeks) and once postpartum (M3: 26 +/- 6 weeks postpartum). We measured muscle sympathetic nerve activity (MSNA), forearm blood flow, and blood pressure at rest and during reactive hyperaemia after forearm occlusion. At M1 and M2, none of the subjects was hypertensive, however, muscle sympathetic nerve activity levels were significantly augmented, compared with their postpartum values (M1: 21 +/- 9, M2: 29 +/- 14, M3: 9 +/- 5 bursts min(-1); P < 0.05). Forearm vascular resistance did not significantly change from M1 through M3 (M1: 16 +/- 9, M2: 15 +/- 7, M3: 16 +/- 7 U; P = NS). Gestational muscle sympathetic nerve activity values did not differ significantly among the subjects with subsequent preeclampsia compared with those who remained normotensive [with preeclampsia (n = 6): M1: 21 +/- 5, M2: 27 +/- 6, M3: 7 +/- 4 bursts min(-1); without preeclampsia (n = 16): M1: 21 +/- 11, M2: 30 +/- 16, M3: 9 +/- 6 bursts min(-1); P = NS]. Invariably, all women at risk for preeclampisa showed a pregnancy-induced increase in MSNA (pregnancy-induced sympathetic overactivity, PISO), which normalized after delivery. Most importantly, PISO is not necessarily associated with peripheral vasoconstriction and hypertension. Furthermore, only a subset of patients developed preeclampsia later on. Therefore, we hypothesize that PISO constitutes a precursor of preeclampsia which is physiologically compensated for by vasodilating mechanisms, leading to preeclampsia only when they fail.

Previous studies suggest that neuronal norepinephrine transporter function may regulate the distribution of sympathetic activity among blood vessels, heart, and kidney; we tested the functional relevance in humans. Sixteen healthy men (261 years) ingested 8 mg of the selective norepinephrine reuptake transporter inhibitor reboxetine or a matching placebo on 2 separate days in a double-blind, randomized, crossover fashion. We monitored

Objective:The endocannabinoid system (ECS) promotes weight gain and obesity-associated metabolic changes. Weight loss interventions may influence obesity-associated risk indirectly through modulation of the peripheral ECS. We investigated the effect of acute and chronic treatment with sibutramine on components of the peripheral ECS.Methods and Procedures:Twenty obese otherwise healthy patients received randomized, double-blind, crossover treatment with placebo and 15 mg/day sibutramine for

Water drinking acutely increases sympathetic activity in human subjects. In animals, the response appears to be mediated through transient receptor potential channel TRPV4 activation on osmosensitive hepatic spinal afferents, described as osmopressor response. We hypothesized that hepatic denervation attenuates water drinking-induced sympathetic activation. We studied 20 liver transplant recipients (4462.6 years, 1.260.1 years post transplant) as model of hepatic denervation and 20 kidney transplant recipients (4362.6 years, 0.860.1 years post transplant) as immunosuppressive drug matched control group. Before and after 500 ml water ingestion, we obtained venous blood samples for catecholamine analysis. We also monitored brachial and finger blood pressure, ECG, and thoracic bioimpedance. Plasma norepinephrine concentration had changed by 0.0160.07 nmol/l in liver and by 0.2160.07 nmol/l in kidney transplant recipients (p,0.05 between groups) after 30-40 minutes of water drinking. While blood pressure and systemic vascular resistance increased in both groups, the responses tended to be attenuated in liver transplant recipients. Our findings support the idea that osmosensitive hepatic afferents are involved in water drinking-induced sympathetic activation in human subjects.