Increase In Peripheral Vascular Resistance Research Articles

Effects of head-up tilting on baroreceptor control in subjects with different tolerances to orthostatic stress.

During orthostatic stress, an increase in peripheral vascular resistance normally results in arterial blood pressure being well maintained, despite a decrease in cardiac output. The present study was undertaken to determine whether the sensitivity of the carotid baroreceptor reflex was increased during orthostatic stress and whether failure to develop this increase was associated with poor orthostatic tolerance. Three groups of subjects were studied: asymptomatic controls; patients investigated for suspected posturally related syncope but who had normal responses to an orthostatic stress test (normal patients); and patients who were shown to have low orthostatic tolerance (early fainters). We determined responses of R-R interval and forearm vascular resistance (mean arterial pressure/brachial artery velocity by Doppler ultrasonography) to the loading and unloading of carotid baroreceptors by application of pressures of -30 and +30 mmHg to a chamber fitted over the neck. Responses were determined after 20 min of supine rest and after 10 min of head-up tilt at 60 degrees. Responses of cardiac interval were not significantly different between the three groups, and they were not altered by the postural change. Vascular responses also did not differ between the groups during supine rest. However, in healthy volunteers and in normal patients, responses to both neck suction and pressure were significantly enhanced during head-up tilt. In controls, responses to suction were increased by tilt from 0.04+/-0.1 to -1.01+/-0.2%.mmHg(-1) (means+/-S.E.M.; P<0.001) and those to neck pressure from -0.6+/-0.3 to -3.1+/-1.1%.mmHg(-1) (P<0.05). In the normal patients, the corresponding changes were: during suction, from -0.2+/-0.1 to -0.7+/-0.1%.mmHg(-1) (P<0.05); during pressure, from -0.7+/-0.1 to -1.5+/-0.3%.mmHg(-1) (P<0.05). In contrast, in patients with low orthostatic tolerance, posture had no effect on the reflex (neck suction, from -0.3+/-0.1 to -0.3+/-0.1%.mmHg(-1); neck pressure, from -1.0+/-0.3 to -0.9+/-0.2%.mmHg(-1)). We suggest that an increase in the sensitivity of the carotid baroreceptor/vascular resistance reflex may be important in the maintenance of blood pressure during orthostatic stress, and that failure of this to occur in patients with posturally related syncope may go some way towards explaining their poor orthostatic tolerance.

Signaling pathways of mechanotransduction in arteriolar endothelium and smooth muscle cells in hypertension.

Hypertension, a disease with a high incidence in the population, affects all parts of the cardiovascular system. Studying the alteration of vasomotor responses of microvessels of hypertensive animals or responses of vessels following short-term increases in hemodynamic forces helps us to better understand the underlying cellular signaling events responsible for their functional adaptation. These adaptations are likely to precede the structural remodeling of arterioles, resulting in irreversible increases in peripheral vascular resistance in hypertension. Although malfunction of several mechanisms can lead to the development of hypertension, hemodynamic forces (such as pressure and shear stress) are increased in all forms of hypertension. Thus, local mechanisms that sense the level of these forces and transduce the signals into vasomotor responses must be affected in all forms of hypertension. The endothelium has a central role in the early functional adaptations. Pressure-induced myogenic constriction is enhanced due to the augmented release of endothelium-derived constrictor factors that modulate arteriolar smooth muscle sensitivity to Ca(2+). In contrast, flow/shear stress-induced dilation of arterioles is reduced in hypertension, due to the impaired mediation of the response by nitric oxide (NO). The magnitude of impairment is gender specific, primarily due to an estrogen-dependent enhancement of NO release in females. It is proposed that the elevated hemodynamic forces present in hypertension may themselves initiate these alterations, probably by enhancing the release of reactive oxygen species (ROS; produced by xanthine oxidase, NAD(P)H oxidoreductase, eNOS, etc.), which then interfere with the synthesis and/or action of endothelium-derived mediators. Interfering early on with these mechanisms may prevent the development of irreversible structural changes of the microcirculation observed in hypertension.

Acute heart failure: a novel approach to its pathogenesis and treatment.

Acute heart failure (HF) is one of the most common syndromes in emergency medicine, however, its exact pathogenesis has remained largely unknown. Based on clinical and hemodynamic data we have sub-divided acute HF into four syndromes: cardiogenic shock, pulmonary edema, hypertensive crisis and exacerbated HF. Cardiogenic shock is caused by a severe reduction in cardiac power which is not met by an adequate increase in peripheral vascular resistance leading to significant decrease in blood pressure and end organ perfusion. Hence the treatment of cardiogenic shock should be directed at improving cardiac performance (by optimizing filling pressure, intra-aortic balloon pump and immediate revascularization) and administration of peripheral vasoconstrictors. The other acute HF syndromes (pulmonary edema, HTN crisis and exacerbated HF) are caused by a combination of progressive excessive vasoconstriction superimposed on reduced left ventricular functional reserve. The impaired cardiac power and extreme vasoconstriction induce a vicious cycle of afterload mismatch resulting in a dramatic reduction of CO and elevated left ventricular end diastolic pressure, which is transferred backwards to the pulmonary capillaries yielding pulmonary edema. Therefore, the immediate treatment of these acute HF syndromes should be based on the administration of strong, fast-acting intravenous vasodilators such as nitrates or nitroprusside. After initial stabilization, therapy should be directed at reducing recurrent episodes of acute HF, by prevention of repeated episodes of excessive vasoconstriction along with efforts to optimize cardiac function.

Diagnosis and treatment of supine hypertension in autonomic failure patients with orthostatic hypotension.

Orthostatic hypotension is seen in various medical conditions. It can be secondary to medications or volume depletion. It can also be due to autonomic neuropathy secondary to other diseases, such as diabetes mellitus, or to primary degenerative processes of the autonomic nervous system. Orthostatic hypotension dominates the clinical picture of patients suffering from autonomic failure. Paradoxically, about one half of these patients also suffer from supine hypertension, which induces pressure natriuresis, worsening orthostatic hypotension. It also complicates the treatment of orthostatic hypotension. Supine hypertension is mediated by an increase in peripheral vascular resistance. This is due to residual sympathetic tone in patients with multiple system atrophy (Shy-Drager syndrome), but the cause is not known in patients with pure autonomic failure, who have increased vascular resistance despite very low levels or plasma norepinephrine and renin activity. The recent observation that patients with supine hypertension develop left ventricular hypertrophy suggests they should be treated. During the day, avoiding the supine position is often all that is required. Short-acting vasodilators (e.g., transdermal nitroglycerin) can be used during the night.

Carotid baroreceptor reflexes in humans during orthostatic stress.

Orthostatic stress, including standing, head-up tilting and lower body suction, results in increases in peripheral vascular resistance but little or no change in mean arterial pressure. This study was undertaken to determine whether the sensitivity of the carotid baroreceptor reflex was enhanced during conditions of decreased venous return. We studied eight healthy subjects and determined responses of pulse interval (ECG) and forearm vascular resistance (mean finger blood pressure divided by Doppler estimate of brachial artery blood velocity) to graded increases and decreases in carotid transmural pressure, effected by a neck suction/pressure device. Responses were determined with and without the application of lower body negative pressure (LBNP) at -40 mmHg. Stimulus-response curves were determined as the responses to graded neck pressure changes and the differential of this provided estimates of reflex sensitivity. Changes in carotid transmural pressure caused graded changes in R-R interval and vascular resistance. The cardiac responses were unaffected by LBNP. Vascular resistance responses, however, were significantly enhanced during LBNP and the peak gain of the reflex was increased from 1.2 +/- 0.3 (mean +/- S.E.M.) to 2.2 +/- 0.3 units (P < 0.05). The increased baroreflex gain may contribute to maintenance of blood pressure during orthostatic stress and limit the pressure decreases during prolonged periods of such stress.

Vascular function and blood pressure in GH transgenic mice.

Acromegaly is associated with cardiovascular disease. We studied vascular function and mean arterial blood pressure in transgenic mice overexpressing bovine GH. Mean arterial blood pressure was measured in conscious, unrestrained male and female bovine GH and littermate control mice during normal as well as high salt intake using telemetric devices. Structure in artificially perfused maximally dilated hindquarter vascular beds and vascular reactivity and endothelial function in small mesenteric vessels were studied in female bovine GH and control mice. Mean arterial blood pressure was increased in female bovine GH transgenic (126 +/- 3 mm Hg) and male bovine GH transgenic (129 +/- 4 mm Hg) compared with female (109 +/- 3 mm Hg, P < 0.05) and male (111 +/- 3 mm Hg, P < 0.05) controls respectively. Increased salt intake had no effect on mean arterial blood pressure. Perfusion studies showed a significant decrease in the average diameter of the female bovine GH transgenic hindquarter vascular bed (P < 0.05). The responses of isolated resistance arteries to nor-epinephrine, potassium-induced depolarization, acetylcholine, or sodium-nitroprusside did not significantly differ between bovine GH transgenic and control mice. We conclude that the phenotype of the bovine GH transgenic mice includes a salt-resistant form of hypertension. Furthermore, the increase in mean arterial blood pressure is accompanied by a significant structural narrowing of the resistance vasculature without changes in vascular reactivity or endothelial function. The results imply that hypertension in bovine GH transgenic mice is maintained mainly by a structurally based increase in peripheral vascular resistance.

Effect of in vivo fetal infusion of dexamethasone at 0.75 GA on fetal ovine resistance artery responses to ET-1.

At 110-111 days gestation, instrumented fetal sheep were administered saline or dexamethasone (2.2 microgram. kg(-1). h(-1) iv) for 48 h. Measurement of fetal blood pressure showed a greater increase in dexamethasone-treated (n = 6) compared with control (n = 5) fetuses (7.3 +/- 2.3 vs. 0.6 +/- 2.3 mmHg, P < 0.05). Fetuses were delivered by cesarean section, and the femoral muscle and brain were obtained under halothane anesthesia. Femoral and middle cerebral arteries (approximately 320-micrometer internal diameter) were evaluated using wire myography. Sensitivity to KCl (2.5-125 mM) and the magnitude of the maximal vasoconstriction to 125 mM K(+) were similar in femoral and middle cerebral arteries from dexamethasone-treated vs. control fetuses. Acetylcholine-induced vasorelaxation was similar in femoral arteries from control and dexamethasone-treated fetuses. Middle cerebral arteries did not relax to acetylcholine. Sensitivity to endothelin-1 (ET-1; 0.1 pM-0.1 microM) and magnitude of the ET-1-induced vasoconstriction were greater in femoral arteries from dexamethasone-treated vs. control fetuses (P < 0.05). Autoradiographical studies with receptor-specific ligands demonstrated increased ET(A)-receptor binding, the principal receptor subtype, in femoral muscle vessels (P < 0.001) but decreased ET(A)-receptor binding in middle cerebral arteries (P < 0.01) from dexamethasone-treated compared with control fetuses. Relatively little ET(B)-receptor binding was evident in all tissues examined. We conclude that hyperreactivity to ET-1, due to increased ET(A)-receptor binding, may be involved in the dexamethasone-induced increase in peripheral vascular resistance in fetal sheep in vivo.

Treatment of Severe Intradialytic Hypotension With the Addition of High Dialysate Calcium Concentration to Midodrine and/or Cool Dialysate

Treatment of intradialytic hypotension (IDH) in the end-stage renal disease population has been a difficult task for nephrologists caring for these patients. The presence of multiple pathogenic factors contributes to hemodynamic instability and explains why therapies that modulate only a specific aspect of the problem are only partially effective. Cool dialysate (34.5°C to 35.5°C) and midodrine may provide hemodynamic stability through an increase in peripheral vascular resistance, whereas high dialysate calcium concentration (HDCa; 3.5 mEq/L) improves intradialytic blood pressure through preservation of cardiac output. Theoretically, the combination of these two types of therapies might further reduce the frequency and severity of hypotension during hemodialysis (HD). We undertook a study to evaluate the effect of HDCa added to midodrine and/or cool dialysate in the treatment of patients with severe IDH. Twenty-eight patients met the entry criteria, and 23 patients completed the prospective crossover study. Five patients dropped out of the study secondary to hypercalcemia. The addition of HDCa significantly improved post-HD mean arterial pressure (MAP; 95.6 ± 12.7 versus 90.8 ± 12.5 mm Hg; P = 0.002). The decreases in MAP from pre-HD to lowest intradialytic (16.3 ± 8.2 versus 20.6 ± 10.0 mm Hg; P = 0.009) and pre-HD to post-HD (2.0 ± 8.5 versus 8.15 ± 10.8 mm Hg; P = 0.002) were significantly reduced with HDCa compared with low dialysate calcium. However, there were no significant improvements in symptoms of or interventions for IDH. Thus, it appears that the addition of HDCa to midodrine and/or cool dialysate further improves blood pressure in patients with IDH. However, this therapy did not reduce symptoms or interventions required for IDH. In addition, hypercalcemia complicated this therapy in 22% of the patients.

Developmental changes in plasma catecholamine concentrations during normoxia and acute hypoxia in the chick embryo.

In the mammalian fetus, the cardiovascular responses to acute hypoxaemia include a redistribution of the cardiac output away from the periphery towards the adrenal, myocardial and cerebral circulations. A component of the peripheral vasoconstriction is mediated by increased release of catecholamines into the fetal circulation during acute hypoxaemia. Previously, we have shown that the chick embryo also shows an increase in peripheral vascular resistance during acute hypoxaemia and that this response becomes progressively larger towards the end of the incubation period. However, the ontogeny of the catecholaminergic response to acute hypoxaemia has not been investigated in this species. Fertilised chicken eggs were studied on days 10, 13, 16 and 19 of incubation (hatching is at 21 days). At each stage of incubation, blood samples were obtained from the chorioallantoic artery of the chick embryos during normoxia and after 5 min of hypoxaemia for measurement of plasma concentrations of adrenaline and noradrenaline by HPLC. Basal plasma adrenaline and noradrenaline concentrations by the end of the incubation period were much higher in the chick embryo than values reported for mammalian fetuses during late gestation. During normoxia, basal plasma noradrenaline concentration remained unchanged during development but plasma adrenaline concentration showed a developmental increase from < 25.1 pmol l-1 at day 10 to 3 nmol l-1 at day 19 of incubation. Acute hypoxaemia caused an increase in plasma noradrenaline and adrenaline from day 13 and day 16 of incubation, respectively. In addition, the increase in plasma adrenaline and noradrenaline and in the ratio of plasma adrenaline to noradrenaline during acute hypoxaemia became progressively larger by the end of the incubation period. These data show an ontogenic increase in basal plasma catecholamines and in the catecholaminergic response to acute hypoxaemia in the chick embryo during the last third of the incubation period.

Pulsatile flow enhances endothelium-derived nitric oxide release in the peripheral vasculature.

The effects of pulsatility in blood flow on endothelium-derived nitric oxide (EDNO) release in the peripheral vasculature were investigated. The basal and flow-stimulated EDNO release were compared between pulsatile and nonpulsatile systemic flows before and after the administration of NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA). Peripheral vascular resistance (PVR) was significantly lower in pulsatile flow than in nonpulsatile flow, but this difference disappeared after L-NMMA. The percent increase in PVR by L-NMMA was significantly larger in pulsatile flow. In reactive hyperemia in the hindlimb, the peak flow did not differ; however, both the repayment flow and the duration were significantly larger in pulsatile flow. Percent changes of these parameters by L-NMMA were significantly larger in pulsatile flow. These data indicated that pulsatility significantly enhances the basal and flow-stimulated EDNO release in the peripheral vasculature under in vivo conditions. We also studied the involvement of the Ca(2+)-dependent and Ca(2+)-independent pathways in flow-induced vasodilation using calmodulin inhibitor calmidazolium and tyrosine kinase inhibitor erbstatin A. PVR was significantly elevated by erbstatin A but not by calmidazolium, suggesting that flow-induced vasodilation was largely caused by tyrosine kinase inhibitor-sensitive activation of NO synthase.

An Association Between QTc Prolongation and Left Ventricular Hypokinesis During Sequential Episodes of Subarachnoid Hemorrhage

An Association Between QTc Prolongation and Left Ventricular Hypokinesis During Sequential Episodes of Subarachnoid Hemorrhage

Intertask consistency of blood pressure responses to laboratory stressors may increase with prolonged exposure

In this study, one of the predictions of the reactivity hypothesis was investigated: the intertask consistency of blood pressure (BP) responses. Twelve young male subjects underwent cold‐pressor (14°C) and digit‐scan (counting even numbers) tests in randomized order. Cardiovascular parameters were recorded during a 2‐min pretask baseline, a 10‐min stressful exposure, and over a 5‐min post‐task baseline. The intertask correlations between the cold pressor and digit scan increased with prolonged exposure and were higher for almost all of the systolic BP measurements than for the diastolic measurements. After prolonged exposure, the hemodynamic mechanisms of BP elevations during the digit scan shifted from an increase in both cardiac output and peripheral vascular resistance to solely an increase in peripheral vascular resistance. Increased peripheral vascular resistance was the consistent cause of the BP elevations with the cold pressor. Accordingly, the hemodynamic shift on the part of the digit scan seemed to heighten the intertask BP correlations. Some other factors influencing the intertask BP correlations are also discussed.

Electrical stimulation of the anterior ethmoidal nerve produces the diving response

Stimulation of the upper respiratory tract usually produces apnea, but it can also produce a vagally mediated bradycardia and a sympathetically mediated increase in peripheral vascular resistance. This cardiorespiratory response, often called the diving response, is usually initiated by nasal stimulation. The purpose of this research was to investigate the anterior ethmoidal nerve (AEN) that innervates the nasal mucosa of muskrats ( Ondatra zibethicus). Electrical stimulation of the AEN (typically 50 Hz, 100 μs and 500 μA) produced immediate and sustained bradycardia and cessation of respiration similar to that of the diving response. Heart rate (HR) significantly decreased from 264±18 to 121±8 bpm, with a concurrent 4.2±0.9 s apnea, during the 5 s stimulation period. BP decreased from 97.9±4.8 to 91.2±6.4 mmHg. Using estimations from (1) cross-sectional areas of AEN trigeminal ganglion cells labeled with WGA-HRP, and (2) electron microscopic analysis of the AEN, we found that approximately 65% of the AEN is composed of unmyelinated C-fibers. In addition, 72.4% of myelinated fibers from the nerves that innervate the nasal passages were of small diameter (<6 μm, presumably Aδ fibers). Thus, the AEN of the muskrat contains a high concentration of small diameter fibers (89.8%). We conclude that electrical stimulation of small diameter fibers within the AEN of muskrats can produce the cardiovascular and respiratory responses similar to that of the diving response.

Obesity and hypertension: from pathophysiology to treatment.

While the prevalence of hypertension is clearly increased among the overweight persons, the pathophysiological mechanisms underlying this frequent association of obesity and hypertension are still poorly understood. The expansion of extracellular volume, inducing hypervolaemia and increased cardiac output, represents the characteristic haemodynamic feature of the obesity-related hypertension. The maintenance of hypervolemia in the face of elevated blood pressure, indicates a resetting of pressor natriuresis toward higher blood pressure. The development of hypertension also indicates an increase in peripheral vascular resistance, thus the lack of physiological adaptation of peripheral resistance to increased cardiac output. The mechanisms underlying these changes in renal function and vascular reactivity can no longer be attributed to hyperinsulinaemia as such, but might be related to insulin resistance responsible for the enhancement in pressor activity of noradrenaline and angiotensin II. This increased reactivity to pressor factors may be due to an inadequate nitric oxide generation by vascular endothelium and to increased sodium and calcium concentration in vascular smooth muscle cells. The role of increased neuropeptide Y (NPY) activity, may also be involved. As to enhancement of tubular sodium reabsorption, it could be related to histological changes within the renal medulla, leading to compression of tubules and vasa recta, hence a more efficient sodium reabsorption. As to the therapeutic approach, the low-energy sodium-restricted diet associated with increased physical activity, represents the cornerstones of treatment for the obesity-related hypertension. If this approach fails, the pharmacological treatment becomes necessary, and the use of the converting enzyme inhibitors seems to be the most appropriate choice of drug therapy for hypertensive obese patients.

Hemodynamic and biochemical effects of 100% oxygen breathing in humans

High concentrations of inspired oxygen have been reported to have significant hemodynamic effects that may be related to increased free radical production. If oxygen therapy increases free radical production, it may also modify hemodynamic responses to a nitric oxide donor. Twenty-nine healthy male volunteers were studied using randomized, double-blind, placebo-controlled, crossover designs to determine whether oxygen therapy is associated with hemodynamic and forearm vascular effects. We measured hemodynamic parameters and forearm vascular responses before and 1 h after exposure to 100% oxygen versus medical air. Plasma 8-iso-PGF2alpha and plasma vitamin C were measured to assess the biochemical effects of oxygen administration. Hemodynamic measurements were also made following the acute administration of sublingual nitroglycerin. Oxygen therapy caused no significant change in blood pressure, plasma 8-iso-PGF2alpha, or vitamin C. Oxygen did cause a significant reduction in heart rate and forearm blood flow, and an increase in peripheral vascular resistance. Oxygen caused no change in the hemodynamic response to nitroglycerin. Therefore, in healthy young adults, therapy with 100% oxygen does not affect blood pressure, despite causing an increase in vascular resistance, is not associated with evidence of increased free radical injury, and does not affect the hemodynamic responses to nitroglycerin.

The role of corticosteriods in the regulation of vascular tone.

Time for primary review 31 days. Disease states resulting from excesses of circulating (adreno)corticosteroids include primary hyperaldosteronism, renal artery stenosis, ACTH-secreting tumors, and administration of glucocorticoids for treatment of other diseases. Hypertension is commonly associated with these diseases. Although renal sodium retention and intravascular volume overload contribute to the attendant hypertension, especially early in the course of the disease, a non-renal mechanism (increase in peripheral vascular resistance) is involved in the development and maintenance of hypertension. The concept of non-renal actions of corticosteroids in the development of hypertension stems from a seminal report in which Langford and Snavely [1]demonstrated that deoxycorticosterone acetate raised blood pressure in dogs and rats devoid of renal mass. In addition, corticosteroids in lesser amounts are essential for the maintenance of peripheral vascular resistance in healthy persons. This review details the proposed mechanisms by which corticosteroids maintain and, in excess, enhance vascular tone. If corticosteroids indeed regulate vascular tone, vascular smooth muscle cells (VSMCs), the vasoactive element of the vasculature, should contain specific receptor molecules for corticosteroids. Classically, corticosteroid receptors are considered to be members of the steroid receptor superfamily of ligand-dependent transcription factors [2]. Radioligand binding studies have defined two distinct cytosolic corticosteroid receptors. Type I (mineralocorticoid) receptors bind with greatest affinity to aldosterone, deoxycorticosterone or corticosterone and with less affinity to the synthetic glucocorticoid dexamethasone. In contrast, type II (glucocorticoid) receptors bind with greatest affinity to dexamethasone and with less affinity to aldosterone, deoxycorticosterone or corticosterone. There is significant base sequence homology between these receptors. Corticosteroid receptors possess highly conserved regions that are necessary for ligand binding, receptor dimerization, nuclear translocation, DNA binding and transactivation (recruiting accessory proteins so that transcription will initiate). The genes for the rat [3, 4]and human [5, 6]mineralocorticoid receptor and the human [7]glucocorticoid receptor … * Tel.: +843-792-4122; fax: +843-792-8399; e-mail: ullianme@musc.edu

Development of analogues: successes and failures.

The search for new pharmaceutical treatments has led to the isolation of products from a range of natural sources. Analogues synthesized from these products may possess an improved therapeutic effect over their natural counterparts. Two natural peptides, vasopressin and somatostatin, possess pronounced in vivo effects, so do their analogues terlipressin and octreotide. Vasopressin is a powerful vasopressor, reducing portal pressure, and has been used to treat gastrointestinal haemorrhages. However, a number of adverse cardiovascular effects resulting from an increase in peripheral vascular resistance have been associated with this drug. Terlipressin, however, is more effective, has an improved safety profile and is associated with fewer side effects than vasopressin. Somatostatin, a growth regulatory hormone, achieves haemostasis by decreasing splanchnic blood flow, and is effective in preventing early rebleeding. Somatostatin is effective in treating bleeding oesophageal varices (BOV) and is associated with fewer and more transient side effects than terlipressin. Octreotide, however, has greater stability and a longer half-life than somatostatin, but has a less favourable safety profile. Octreotide displays a number of therapeutic advantages over somatostatin, but not in the treatment of gastrointestinal indications. The development of terlipressin from vasopressin has demonstrated a number of clinical advantages, while the development of octreotide from somatostatin has not shown any significant advantage in the treatment of BOV.

Cardiopulmonary and arterial baroreflex-mediated control of forearm vasomotor tone is impaired after acute stroke.

Elevated blood pressure (BP) levels are well recognized after acute stroke and are associated with increased BP variability. The underlying mechanisms producing such changes are unclear but may include abnormalities of baroreceptor-mediated control of heart rate and vasomotor tone. Lower body negative pressure (LBNP) can be used to assess the integrity of "low-pressure" cardiopulmonary and "high-pressure" arterial baroreceptor-derived responses by inducing nonhypotensive and hypotensive stimuli. Cardiovascular responses, including BP, heart rate, forearm blood flow, and forearm vascular resistance, to nonhypotensive and hypotensive LBNP were assessed in 13 consecutive stroke patients. Patients were studied within 72 hours of stroke (acute) and again at 10 to 14 days (subacute) and were compared with 13 control subjects individually matched for age, sex, and BP. At an LBNP of -10 mm Hg, BP was unchanged in all groups, but a significant increase in forearm vascular resistance occurred only in the control group (11 U [interquartile range, 7 to 15]; P < .05) compared with stroke patients in the acute (9 U [3 to 14]; P = NS) or subacute phases (7 U [2 to 12]; P = NS). After LBNP at -40 mm Hg, the reductions in systolic BP levels were similar in all groups (control: -9 mm Hg [-16 to -3]; acute stroke: -9 mm Hg [-22 to 3]; subacute stroke: -7 mm Hg [-35 to 20]), as was the associated increase in heart rate (control: 8 bpm ([4 to 11]; acute stroke: 6 bpm ([1 to 12]; subacute stroke: 9 bpm [2 to 19]). However, forearm vascular resistance increased significantly only in control subjects (20 U [9 to 30]; P < .01). The present study has identified abnormal vasomotor responses to LBNP after acute stroke, with an increase in FVR only being observed in control subjects in response to nonhypotensive and similar hypotensive levels of LBNP. In acute stroke patients, the stimulus of hypotensive LBNP appears to be compensated by an increase in cardiac output since there appears to be no increase in peripheral vascular resistance, unlike the changes seen in control subjects. However, the exact mechanisms for these changes are still unclear and are the subject of further study.

Effects of hibernation on neural and endothelial control of mesenteric arteries of the golden hamster.

The effects of hibernation on mesenteric arterial innervation and function were examined using pharmacological and immunohistochemical techniques in age-matched controls, cold-exposed controls, and 4-wk-hibernated golden hamsters. Electrical field stimulation of the isolated mesenteric arterial bed elicited frequency-dependent vasoconstriction. The sensitivity of responses was significantly increased in tissues from hibernating animals compared with cold-exposed controls. Vasoconstrictor responses to exogenous norepinephrine were also increased in hibernation. However, there was a significant decrease in sensitivity of vasoconstriction to ATP in hibernated and cold-exposed tissue compared with age-matched controls. In preparations preconstricted with methoxamine, endothelium-dependent vasodilator responses to acetylcholine and ATP were similar among the groups. Immunohistochemical investigation of mesenteric arteries revealed no differences among the groups in density of innervation by nerves immunoreactive for tyrosine hydroxylase, neuropeptide Y, and calcitonin gene-related peptide. Postjunctional changes appear to occur in hibernation, leading to augmentation of sympathetic vasoconstriction, which is consistent with the increase in peripheral vascular resistance in hibernation. Endothelium-dependent vasodilatation is not significantly changed in hibernation in the hamster mesenteric arterial bed.

Preeclampsia-A State of Sympathetic Overactivity

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...