Showing papers by "Roland E. Schmieder published in 1996"
TL;DR: In this first meta-analysis including only double-blind, randomized, controlled clinical studies, decline in blood pressure, duration of drug treatment, and drug class determined the reductions in left ventricular mass index.
Abstract: Objective. —To determine the ability of various antihypertensive agents to reduce left ventricular hypertrophy, a strong, blood pressure—independent cardiovascular risk factor, in persons with essential hypertension. Data Sources. —MEDLINE, DIMDI, RINGDOC, ADES, EMBASE, and review articles through July 1995 (English-language and full articles only). Study Selection. —Meta-analysis of all published articles including only double-blind, randomized, controlled clinical studies with parallel-group design. Data Extraction. —Intensive literature search and data extraction according to a prefixed scheme performed independently by 2 investigators. Reduction of left ventricular mass index after antihypertensive therapy with placebos, diuretics, β-blockers, calcium channel blockers, or angiotensin-converting enzyme (ACE) inhibitors was the principal parameter. Data Synthesis. —Of 471 identified references describing the effects of antihypertensive drugs on left ventricular hypertrophy, only 39 clinical trials fulfilled the inclusion criteria of our study. We found that the decrease in left ventricular mass index was more marked the greater was the decline in blood pressure (systolic r =0.46, P r =0.21, P =.08) and the longer was the duration of therapy ( r =0.38, P P P P =.08). Similar differences between drug classes were found with regard to effect on left ventricular wall thickness ( P Conclusions. —The database of articles published through July 1995 is small and incomplete, and most of the articles are of poor scientific quality. In this first meta-analysis including only double-blind, randomized, controlled clinical studies, decline in blood pressure, duration of drug treatment, and drug class determined the reductions in left ventricular mass index. The ACE inhibitors seemed to be more potent than β-blockers and diuretics in the reduction of left ventricular mass index; calcium channel blockers were somewhat in the intermediate range. The ACE inhibitors and, to a lesser extent, calcium channel blockers emerged as first-line candidates to reduce the risk associated with left ventricular hypertrophy. ( JAMA . 1996;275:1507-1513)
632 citations
TL;DR: Preeclampsia is a state of sympathetic overactivity, which reverts to normal after delivery, which indicates that the increases in peripheral vascular resistance and blood pressure that characterize this disorder are mediated, at least in part, by a substantial increase in sympathetic vasoconstrictor activity.
Abstract: Background Preeclampsia is characterized by a marked increase in peripheral vascular resistance leading to an increase in blood pressure, but the triggering mechanisms are unclear. Methods To determine whether augmented sympathetic vasoconstrictor activity may be an important mechanism in mediating the increase in vasomotor tone, we measured postganglionic sympathetic-nerve activity in the blood vessels of skeletal muscle by means of intraneural microelectrodes in nine women with preeclampsia, eight normotensive pregnant women, six normotensive nonpregnant women, and seven nonpregnant women with hypertension, both at rest and during noninvasive cardiovascular-reflex testing (with the Valsalva maneuver and the cold pressor test). Results The mean (±SE) rate of sympathetic-nerve activity in the normotensive pregnant women (10±1 bursts per minute) was not significantly different from that in normotensive nonpregnant women (12±2 bursts per minute) or hypertensive nonpregnant women (15±3 bursts per minute). In...
550 citations
TL;DR: Impaired suppression of the renin-Ang II system appeared to act as a stimulus for myocardial hypertrophy in hypertensive patients.
Abstract: Background Urinary sodium excretion and angiotensin II (Ang II), which are linked in a physiological feedback mechanism, have both been described to be blood pressure-independent determinants of left ventricular hypertrophy in essential hypertension. We conducted a study to investigate the interaction of sodium excretion with Ang II and its potential impact on myocardial hypertrophy. Methods and Results Sixty-eight patients (46 men and 22 women; mean age, 52±10 years) with untreated World Health Organization stage I to II essential hypertension were examined in a cross-sectional study. Left ventricular structure and function (two-dimensionally guided M-mode echocardiography), dietary sodium intake (as estimated by 24-hour urinary sodium excretion), and noninvasive ambulatory blood pressure over 24 hours (Spacelab 90207) were determined in parallel with plasma renin activity and plasma Ang II and serum aldosterone concentrations (radioimmunoassay). Twenty-four-hour urinary sodium excretion emerged as a str...
144 citations
TL;DR: The increased pain tolerance in human hypertension cannot be explained by hemodynamically mediated differences in the activation of baroreceptors or by an altered baroreflex sensitivity during the application of pain.
Abstract: Observations in animals and humans show that pain sensitivity might be lower (and pain tolerance higher) in hypertensive as compared to normotensive subjects. One hypothesis, derived from experimental studies, assumes that enhanced activation of baroreceptors leads to an enhanced central inhibition. A central hypothesis assumes changes in the central (endogenous) control of the nociceptive system. To investigate these two hypotheses we quantitatively assessed the minute-by-minute changes in mean arterial pressure (MAP), central venous pressure (CVP) heart rate (HR), muscle sympathetic nerve activity (MSNA), and individual pain ratings during noxious mechanostimulation in 10 normotensive (NT) and 13 borderline hypertensive (BH) subjects. Linear regression analysis indicated a close negative correlation for the overall data between resting levels of MAP and pain ratings (r = −0.57, P < 0.0001). The BH group exhibited a lower pain sensitivity compared to the NT group (P < 0.001). The extent of baroreceptor activation during the application of pain was not different between the two groups (P = NS) as assessed by almost identical increases in MAP (+8 ± 1 vs. +9 ± 1 mmHg NT vs. BH group), CVP (+0.7 ± 0.1 vs. +0.5 ± 0.1 mmHg), HR (+2 ± 1 vs. +2 ± 1 beats/min), and MSNA (+5 ± 1 vs. +4 ± 1 bursts/min). The NT subjects exhibited significant correlations between the pain ratings and the increases in MAP (r = +0.52; P < 0.05) and MSNA (r = +0.49; P < 0.05) whereas the BH subjects did not show such a relationship. Thus, the increased pain tolerance in human hypertension cannot be explained by hemodynamically mediated differences in the activation of baroreceptors or by an altered baroreflex sensitivity during the application of pain. We conclude, that the reduced pain sensitivity in hypertensive humans is more likely related to central changes.
66 citations
TL;DR: It is concluded that endogenous Ang II modulates the renal effects of centrally mediated changes of sympathetic nerve activity in conscious rats and impaired or abolished the renal nerve-mediated antinatriuresis and anitidiuresis in response to air-jet stress.
Abstract: A putative interaction between angiotensin II (Ang II) and the sympathetic nervous system within the kidney has been reported. We tested the hypothesis in conscious rats that endogenous Ang II modulates the renal effects of a stress-induced increase in sympathetic nerve activity. We recorded mean arterial blood pressure, heart rate, renal sympathetic nerve activity, renal hemodynamics, urine volume, and urinary sodium content in conscious rats. We used the Ang II type 1 receptor blocker ZD 7155 to inhibit the effects of endogenous Ang II. Ten minutes of air-jet stress increased renal sympathetic nerve activity by 98±4% (n=6) without changing systemic hemodynamics. Air-jet stress reduced urine volume (from 31±3 to 8±4 μL/min per gram kidney weight, P P
35 citations
TL;DR: It is concluded that cardiac bradykinin elicits a sympathoexcitatory reflex by epicardial B2 receptors in rats, and the afferent portion of the reflex is most likely contained within sympathetic cardiac afferent fibers.
Abstract: Bradykinin may be generated in the heart during ischemia and is involved in nociception. We tested the hypothesis that bradykinin elicits a sympathoexcitatory reflex in rats by stimulating cardiac afferent nerve fibers. Rats were implanted with femoral catheters for measurement of blood pressure and heart rate, a bipolar electrode for measurement of renal sympathetic nerve activity, and a pericardial catheter for intrapericardial injection of substances. Rats were slightly anesthetized with hexobarbital so pain reactions were prevented. Graded doses of bradykinin (2.5, 12, 25 micrograms) were injected intravenously or intrapericardially into control rats, intrapericardially after vagotomy, intrapericardially after intrapericardial pretreatment with the bradykinin B2 receptor antagonist Hoe 140, and intrapericardially after cardiac autonomic blockade (intrapericardial pretreatment with 10% procaine). For comparison, the serotonin 5-HT3 agonist phenylbiguanide, a substance known to elicit sympathoinhibitory reflexes by cardiac vagal afferents, and adenosine, putatively inducing sympathoexcitatory responses via the heart, were applied intrapericardially. Bradykinin increased blood pressure when administered intrapericardially but decreased blood pressure when injected intravenously; both intrapericardial and intravenous bradykinin increased renal sympathetic nerve activity. Intrapericardial adenosine had no effect on circulatory control. Intrapericardial pretreatment with the B2 receptor antagonist Hoe 140 completely inhibited the increases of blood pressure and renal sympathetic nerve activity in response to intrapericardial bradykinin but did not affect the responses to intrapericardial phenylbiguanide. Bilateral cervical vagotomy abolished the decreases of blood pressure, heart rate, and renal sympathetic nerve activity after intrapericardial phenylbiguanide but did not influence the responses to intrapericardial bradykinin. Cardiac autonomic blockade with intrapericardial procaine abolished all responses to bradykinin and phenylbiguanide. We conclude that cardiac bradykinin elicits a sympathoexcitatory reflex by epicardial B2 receptors in rats. The afferent portion of the reflex is most likely contained within sympathetic cardiac afferent fibers. Bradykinin may contribute to increased sympathetic nerve activity in pathophysiological situations of coronary artery disease and cardiac ischemia.
25 citations
TL;DR: A double-blind, randomized, controlled clinical trial to compare the effects of α-blockers and β-blocker medication on left ventricular structure and function in essential hypertension found neither metoprolol nor bunazosin significantly affectedleft ventricular systolic function.
23 citations
TL;DR: A series of clinical trials found that α1-receptor antagonists reduced left ventricular hypertrophy, lowered total peripheral resistance, improved glomerular filtration rate, and had no effect or improved lipid metabolism, glucose tolerance, and insulin resistance, which emerged as attractive agents for antihypertensive therapy.
16 citations
TL;DR: It is concluded that 5-HT3-serotonergic cardiopulmonary chemoreceptors blunt the RSNA decrease to volume loading, which may facilitate volume retention when cardiac serotonin is increased.
Abstract: Volume-sensitive and chemosensitive cardiopulmonary reflexes modulate volume homeostasis via renal sympathetic nerve activity (RSNA). Blunting of volume-sensitive cardiopulmonary reflexes is associated with volume retention, e.g., in hypertension, whereas the role of chemosensitive cardiopulmonary reflexes is largely unknown. To elucidate the possible role of chemosensitive cardiopulmonary reflexes in control of volume homeostasis, we investigated whether subthreshold stimulation of 5-HT3 receptors modulates the control of RSNA by volume-sensitive cardiopulmonary reflexes or the arterial baroreceptor reflex in rats. Phenyl biguanide (PBG) was infused intravenously to stimulate 5-HT3 receptors. Higher doses of PBG lowered RSNA, but a dose of 6 micrograms/min, given as a background infusion throughout the experiment, did not change arterial pressure, heart rate (HR), or RSNA. Ten minutes after beginning the 6 micrograms/min PBG infusion, a 15-min volume expansion (0.9% saline, 5 or 10% body weight) was started to stimulate volume-sensitive cardiopulmonary reflexes. In separate experiments, 5-min ramp infusions of methoxamine and nitroglycerin to stimulate the arterial baroreceptor reflex (evaluated by a 4-parameter logistic regression) were performed 15 min after beginning the PBG background infusion (6 micrograms/min). During PBG infusion, the RSNA responses to volume expansions were significantly impaired (5% body weight: PBG -6 +/- 6%, n = 7 vs. control -39 +/- 9%, n = 6, P < 0.001; 10% body weight: PBG -33 +/- 6%, n = 8 vs. control -52 +/- 5%, n = 7, P < 0.05). The 5-HT3 receptor antagonist odansetron (GR-38032F) abolished these effects of PBG. The maximum HR gain of the arterial baroreceptor reflex was impaired but the arterial baroreceptor control of RSNA was unaffected by PBG background infusion. We conclude that 5-HT3-serotonergic cardiopulmonary chemoreceptors blunt the RSNA decrease to volume loading. This mechanism may facilitate volume retention when cardiac serotonin is increased.
14 citations
TL;DR: Mental stress as a correlate of daily life stress appeared not to confound the selective renal vasodilatory effect of ACE inhibitors, which is conserved during mental stress without persistent effects on the sympathetic nervous system.
Abstract: OBJECTIVE To examine the effects of angiotensin converting enzyme (ACE) inhibition on renal and systemic haemodynamics as well as on humoral regulators, under resting conditions and during mental stress in 20 normotensive and 20 mildly hypertensive subjects. METHODS All of the subjects received either 25 mg cilazapril or placebo once a day, in a randomized, double-blind, cross-over trial for 1 week, followed by a 2-week washout period before the alternative regimen was given. We measured renal blood flow with para-aminohippuran, glomerular filtration rate with inulin, cardiac output by impedance cardiography and blood pressure and heart rate by an oscillometric method. We also monitored effects on plasma renin activity, aldosterone, catecholamines and atrial natriuretic peptide. Mental stress consisted of a long-lasting, time-reaction device, thereby provoking activation of the sympathetic nervous system. RESULTS At rest ACE inhibition lowered mean arterial pressure (92 +/- 10 versus 98 +/- 9 mmHg), increased renal blood flow (803 +/- 109 versus 707 +/- 93 ml/min) and the renal fraction of cardiac output (25.9 +/- 2.5 versus 23.5 +/- 2.5%) and decreased the filtration fraction (17.9 +/- 2.5 versus 19.8 +/- 2.7%) in hypertensive but not in normotensive subjects. Sympathetic activation by mental stress leading to a transient increase in blood pressure did not alter significantly the effects of ACE inhibition on renal and systemic haemodynamics, in normotensive or in hypertensive subjects, although a tendency towards attenuation of the rise in glomerular filtration rate was noted in hypertensives (7.2 +/- 1.0 versus 5.1 +/- 0.8%). ACE inhibition led to increased plasma noradrenaline at rest but not during mental stress in hypertensive patients. CONCLUSION ACE inhibition in patients with mild hypertension increased selectively renal perfusion, which is conserved during mental stress without persistent effects on the sympathetic nervous system. Thus, mental stress as a correlate of daily life stress appeared not to confound the selective renal vasodilatory effect of ACE inhibitors.
11 citations
Journal Article•
TL;DR: Despite an initially higher susceptibility to orthostatic stress under a provocative manoeuver, bunazosin evoked the same low incidence of Orthostatic dysregulation symptoms as nitrendipine under daily life conditions, but was significantly better tolerated than nitrendipsine.
Abstract: A multicentre double-blind randomized controlled study was conducted in 358 patients with mild to moderate essential hypertension. The goal was to compare the antihypertensive efficacy, tolerability, and in particular postural hypotension of the alpha 1-adrenoreceptor blocker bunazosin with the calcium channel blocker nitrendipine. Both treatment groups had comparable baseline blood pressure (BP) values, namely diastolic BP (DBP) of 103.8 +/- 5.6 mm Hg in the bunazosin group, and 103.4 +/- 6.0 mm Hg in the nitrendipine group, respectively. Baseline systolic BPs (SBP) were 149.7 +/- 14.4 mm Hg (bunazosin) and 149.2 +/- 14.3 mm Hg (nitrendipine). After 12 weeks of therapy, reduction of DBP (-6.1 +/- 11.7 mm Hg on bunazosin vs -6.9 +/- 9.9 mm Hg on nitrendipine; P = n.s.), and SBP (-4.4 +/- 14.3 mm Hg on bunazosin vs -7.0 +/- 14.4 mm Hg on nitrendipine; P = n.s.) was similar in both groups. During a provocative orthostatic tolerance test after the first dose, the incidence of prae-collapses (ie termination of the test due to orthostatic complaints) was higher on bunazosin (17 vs 2; P < 0.05) but orthostatic dysregulation symptoms (symptom score 1.37 on bunazosin vs 0.95 on nitrendipine; n.s.) and collapses (four on bunazosin vs one on nitrendipine; n.s.) occurred to a similar extent in both treatment groups. Three and 9 weeks after treatment, no increased susceptibility to orthostatic stress compared to baseline could be found in either group. Under daily life conditions, the frequency of orthostatic dysregulation was identical in both groups (0.8%). Bunazosin, however, was far better tolerated with 43.8% of the patients complaining of adverse events as opposed to 63.6% on nitrendipine (P < 0.001). The rate of early discontinuations due to adverse events was only 1.3% on bunazosin compared to 13.6% on nitrendipine (P < 0.001). In conclusion, bunazosin has a similar antihypertensive efficacy as nitrendipine. Despite an initially higher susceptibility to orthostatic stress under a provocative manoeuver, bunazosin evoked the same low incidence of orthostatic dysregulation symptoms as nitrendipine under daily life conditions, but was significantly better tolerated than nitrendipine.
TL;DR: The aim of the meta-analysis was to elucidate clinical determinants for the regression of left ventricular hypertrophy in essential hypertension by choosing treatment arms as units in a single study to break the "matching" of study arms with different treatments.
Abstract: In Reply. —The aim of our meta-analysis was to elucidate clinical determinants for the regression of left ventricular hypertrophy in essential hypertension. Different drug classes were evaluated with respect to their ability to reduce left ventricular mass. 1 Since none of the double-blind, randomized, clinical trials compared all drug arms in a single study, we decided to choose treatment arms as units in our metaanalysis. Potential criticisms of this procedure might be that treatment arms of different studies are not comparable and that the "valid n" of our meta-analysis is thereby artificially increased. If 2 or more groups are compared, it is essential that within each group the results are independent. If one ignores an existing positive correlation, the result indeed is an overestimation of statistical precision. However, that was definitely not what we did. Instead, we broke the "matching" of study arms with different treatments, and the meta-analysis is more likely
TL;DR: The LV mass has been shown to correlate better with 24-hour blood pressure measurements than with spot measurements and has been clearly identified as a surrogate endpoint for cardiovascular morbidity and mortality, which are far more meaningful than blood pressure.
Abstract: To the Editor. —In their meta-analysis of RCTs, Midgley et al 1 found a rather disappointing effect of dietary sodium restriction on blood pressure. Based on these findings, the authors question the wisdom of a sodium restriction in the general population and to a lesser extent in the hypertensive population. However, blood pressure is merely a surrogate endpoint that often, but not always, correlates with the real endpoints, ie, cardiovascular morbidity and mortality. Blood pressure also is an extremely variable measurement that is affected by myriad endogenous and exogenous pathophysiological factors throughout a 24-hour period. A parameter that more consistently reflects the average blood pressure load is LV wall thickness or LV mass. The LV mass has been shown to correlate better with 24-hour blood pressure measurements than with spot measurements and has been clearly identified as a surrogate endpoint for cardiovascular morbidity and mortality, which are far more meaningful than blood pressure
TL;DR: It seems impossible to separate the effect of antihypertensive agents per se from the effects of the intensive nonpharmacological intervention plus drug therapy, since interactions between the 2 therapeutic strategies most likely occurred.
Abstract: In Reply. —Dr Liebson and colleagues criticized that TOMHS 1 was not included in our meta-analysis on reversal of left ventricular hypertrophy in essential hypertension. The primary goal of the meta-analysis was "to determine the ability of various antihypertensive agents to reduce left ventricular hypertrophy." In the TOMHS trial, nutritional-hygienic treatment was compared with a combination of drug treatment and nutritional-hygienic intervention. Therefore, it seems impossible to separate the effect of antihypertensive agents per se from the effects of the intensive nonpharmacological intervention plus drug therapy, since interactions between the 2 therapeutic strategies most likely occurred. For instance, nonpharmacological intervention, including restriction of dietary salt intake and reduction of overweight in combination with a diuretic, resulted in a more marked decrease of left ventricular end-diastolic diameter than with other antihypertensive drugs (-0.7 mm vs -0.3 mm; P 1 Whether the effect of the diuretic was attenuated or potentiated by the nonpharmacological