Changes In Total Peripheral Resistance Research Articles

Hemodynamic of Post-Dynamic Submaximal Exercise in Obese Women with and without Type 2 Diabetes

1459 PURPOSE: Post-exercise hypotension (PEH) is the decrease in resting systolic blood pressure (SBP) after an acute bout of exercise. PEH has been attributed to decreases in vascular resistance and cardiac output in hypertensives but hemodynamic responses may differ in other clinical populations. To evaluate the hemodynamic contributors to the hypotensive effect of a single bout of dynamic exercise in obese women (30.1–43.4 kg/m2, 45–59 years) with (n = 8) and without (n = 9) type 2 diabetes (T2D). METHODS: We evaluated SBP, total peripheral resistance (TPR), stroke volume (SV), heart rate (HR), and cardiac output at pre-exercise and at 10, 20, and 30 min after 20 min of treadmill exercise at 65% of VO2 max. Hemodynamic variables were measured using beat-to-beat finger plethysmography (Portapres) in the supine position. Data were analyzed using an ANOVA with repeated measures (pre-exercise, 10, 20, and 30 min post-exercise). RESULTS: SBP was significantly (p<.05) reduced from pre-exercise at 10–30 min into recovery in the obese group but not in the T2D group. SBP changes from pre-exercise to 30 min post-exercise were significantly (p<.05) greater in the obese group (− 9 ± 10 mm Hg) compared to the T2D group (3 ± 11 mm Hg). Both groups demonstrated a similar change in TPR during recovery with a reduction at 10 min followed by a significant (p<.05) increase at 30 min post-exercise. SV was significantly (p<.05) reduced from pre-exercise at 10–30 min post-exercise in both groups without significance between groups. HR was significantly (p<.05) increased from pre-exercise at 10 and 20 min but not at 30 min post-exercise in both groups. Cardiac output changed significantly (p<.05) from pre-exercise values to the lowest level at 30 min post-exercise in the obese (− 0.7 ± 0.7 L/min) and T2D (− 0.5 ± 0.9 L/min) (p = .09 for group × condition interaction). CONCLUSIONS: These findings indicate that PEH during 30 min after submaximal exercise is observed in obese women without T2D but not in obese women with T2D. PEH in obese women without T2D is mediated primarily by a reduction in cardiac output due to a large decrease in SV. The higher SBP at 30 min post-exercise in T2D women was primarily due to lower decrease in cardiac output, since the increase in TPR was similar in both groups. Sponsored by NY State Diabetes Bridge Grant

Spontaneous beat-by-beat fluctuations of total peripheral and cerebrovascular resistance in response to tilt.

Beat-by-beat estimates of total peripheral resistance (TPR) can be obtained from continuous measurements of cardiac output by using Doppler ultrasound and noninvasive mean arterial blood pressure (MAP). We employed transfer function analysis to study the heart rate (HR) and vascular response to spontaneous changes in blood pressure from the relationships of systolic blood pressure (SBP) to HR (SBP-->HR), MAP to total peripheral resistance (TPR) and cerebrovascular resistance index (CVRi) (MAP-->TPR and MAP-->CVRi), as well as stroke volume (SV) to TPR in nine healthy subjects in supine and 45 degrees head-up tilt positions. The gain of the SBP-->HR transfer function was reduced with tilt in both the low- (0.03-0.15 Hz) and high-frequency (0.15-0.35 Hz) regions. In contrast, MAP-->TPR transfer function gain was not affected by head-up tilt, but it did increase from low- to high-frequency regions. The phase relationships between MAP-->TPR were unaffected by head-up tilt, but, consistent with an autoregulatory system, changes in MAP were followed by directionally similar changes in TPR, just as observed for the MAP-->CVRi. The SV-->TPR had high coherence with a constant phase of 150-160 degrees. Together, these data that showed changes in MAP preceded changes in TPR, as well as a possible link between SV and TPR, are consistent with complex interactions between the vascular component of the arterial and cardiopulmonary baroreflexes and intrinsic properties such as the myogenic response of the resistance arteries.

Does whole body autoregulation mediate the hemodynamic responses to increased dietary salt in rats with clamped ANG II?

The present study was conducted to test the hypothesis that salt-dependent hypertension, in rats with an unresponsive renin-angiotensin system, is characterized by a "whole body autoregulation" hemodynamic profile. To test this hypothesis, rats were chronically instrumented to continuously measure cardiac output (CO) and arterial pressure (AP). A venous catheter was implanted for infusion of saline vehicle (Veh; n = 8) or treatment [enalapril (2 mg.kg-1.day-1) plus ANG II: ANG-NORM (5 ng.kg-1.min-1 ANG II, n = 8) or ANG-HI (10 ng.kg-1.min-1 ANG II, n = 9)] to pharmacologically clamp plasma ANG II. After a 10-day recovery period on a 0.1% NaCl diet, AP and CO were measured continuously for 5 days of control (0.1% NaCl), 7 days of high salt (4.0% NaCl), and 5 days of recovery (0.1% NaCl). Hemodynamics did not change in the Veh group at any time. AP increased by approximately 20 mmHg in the ANG-NORM and ANG-HI groups when NaCl was increased. Hypertension was mediated by an increase in CO of approximately 12% at steady state, with no change in total peripheral resistance (TPR) during the high salt period. AP returned to control levels when dietary sodium was decreased, mediated by a approximately 10% decrease in TPR, with CO remaining elevated. There was no difference in the hemodynamic responses to increased salt between the ANG-HI and ANG-NORM groups. We conclude that the whole body autoregulation hypothesis does not explain the hemodynamic profile of salt-dependent hypertension in rats with an unresponsive renin-angiotensin system.

Midodrine Improves Chronic Hypotension in Hemodialysis Patients

The effects of midodrine on chronic hypotension in hemodialysis (HD) patients have not been well investigated. We evaluated midodrine's effect on autonomic function and hemodynamics in 12 HD patients who had chronic systolic blood pressure less than 100 mm Hg. Midodrine (5.0 mg) twice a day was given for 4 weeks. Another 12 age- and sex-matched HD patients with normotension were selected as a control group. Autonomic function tests included the heart-rate responses to the Valsalva maneuver and 30:15 ratio as well as supine and standing blood pressure (BP) and sustained hand-grip test. Hemodynamic changes included 24-hour blood pressure, cardiac output, total peripheral resistance (TPR), and plasma renin and aldosterone concentrations. Compared with the control subjects, HD patients with chronic hypotension had more severe autonomic dysfunction and significantly lower TPR. After 4 weeks of midodrine therapy, sympathetic function (orthostatic and hand-grip tests) improved in conjunction with significant increases in mean arterial pressure (MAP) (79.5 +/- 4.9 to 85.0 +/- 5.1 mm Hg, P < 0.05) and TPR (768 +/- 37 versus 1097 +/- 72 dyne/sec/cm-5, P < 0.01) despite no significant change in Valsalva ratio, 30:15 ratio, and cardiac output. MAP changes were positively correlated with TPR changes (r = 0.82, P < 0.001). Supine plasma renin activity was significantly increased. In addition, MAP during HD was also significantly increased during midodrine therapy. Midodrine improves chronic hypotension in HD patients by modulating autonomic function and its direct effects on peripheral vessels.

Early vascular abnormalities and de novo nitrate tolerance in diabetes mellitus.

The haemodynamic consequence of altered mechanical wall properties in diabetes can impair the compliance characteristics or pulsatile function of arteries before changes in calibre or peripheral resistance become evident. We studied the sensitivity of pulsatile and steady-state haemodynamic variables in identifying vascular abnormalities and assessing arterial responsiveness to glyceryl trinitrate (GTN) in patients with diabetes, free from clinical complications of the disease. Radial artery pressure waveforms were recorded in 22 patients with diabetes and 22 age- and sex-matched control subjects, using a calibrated tonometer device. A computer-based assessment of the diastolic pressure decay was used to quantify changes in arterial waveform morphology in terms of pulsatile (arterial compliance) and steady-state (peripheral resistance) haemodynamics. Pressure pulse waveforms were recorded before and 3, 6 and 9 min after the administration of 300 micro g of GTN. Of the pulsatile and steady-state impedance parameters, only small artery compliance was significantly different in patients, 4.7 ml/mmHg (95% CI 3.8-5.8), compared with control subjects 7.1 ml/mmHg (95% CI 5.4-8.7); (p < 0.05). In response to GTN small artery compliance increased, and systemic vascular resistance decreased significantly in control subjects; (p < 0.05) but remained unchanged in patients with diabetes. Arterial waveform analysis proved more sensitive in detecting early vascular abnormalities and tracking the haemodynamic effects of GTN in patients with diabetes than changes in total peripheral resistance. The diminished responsiveness of the arterial vasculature to organic nitrates may have therapeutic implications for the treatment of cardiovascular disease in diabetes mellitus.

Stability of access resistance during haemodialysis

Access blood flow (Qac) is considered a useful indicator in the surveillance of haemodialysis access function. However, changes in Qac may be due to changes in blood pressure and/or to changes in access resistance (AR).Weekly readings of Qac, cardiac output, and arterial blood pressure measured early and late during haemodialysis were obtained in 11 patients for a period of 3 weeks. Qac was determined from thermodilution of extracorporeal blood returning to the patient with reversed placement of blood lines and by measurement of arterial and venous blood temperatures in the extracorporeal circulation. Data are given as mean +/- SE.Qac dropped as mean arterial pressure (MAP) and total peripheral resistance (TPR) decreased, but increased when MAP and TPR increased. Linear regressions between the change in access flow and the change in MAP (deltaQac%=0.80*deltaMAP%-1.6, r2=0.39), and the change in TPR (deltaQac%= 0.54*deltaTPR%-9.2, r2=0.35) respectively, were significant (P<0.001). Whereas Qac significantly decreased (-8.4+/-3.3%, P<0.01) during the same treatment, AR remained unchanged (4.7+/-3.2%; P=NS). AR for all studies was 16.5+/-1.0 peripheral resistance units (1 PRU=2.226 kPa min l(-1)). There was a trend for resistance to increase (5.1+/-2.6%, P=NS) and for flow to decrease (-6.1+/-2.3%, P=NS) during the 3 weeks of the study.Qac measured during haemodialysis is variable and depends on haemodynamics, but AR is constant. AR is related to the physical structure of the peripheral access. Because of its intradialytic stability AR may be better suited as an indicator of access function.

System identification of dynamic closed-loop control of total peripheral resistance by arterial and cardiopulmonary baroreceptors

Prolonged exposure to microgravity in space flight missions (days) impairs the mechanisms responsible for defense of arterial blood pressure (ABP) and cardiac output (CO) against orthostatic stress in the post-flight period. The mechanisms responsible for the observed orthostatic intolerance are not yet completely understood. Additionally, effective counter measures to attenuate this pathophysiological response are not available. The aim of this study was to investigate the ability of our proposed system identification method to predict closed-loop dynamic changes in TPR induced by changes in mean arterial pressure (MAP) and right atrial pressure (RAP). For this purpose we designed and employed a novel experimental animal model for the examination of arterial and cardiopulmonary baroreceptors in the dynamic closed-loop control of total peripheral resistance (TPR), and applied system identification to the analysis of beat-to-beat fluctuations in the measured signals.

Role of endothelin and vasopressin in DOCA-salt hypertension.

1. The relative roles of endothelin (ET) and vasopressin (AVP) in the regulation of blood pressure (BP), cardiac output (CO) and total peripheral resistance (TPR) were investigated in the early stages (24 - 31 days) of development of hypertension in the conscious deoxycorticosterone acetate (DOCA)-salt hypertensive rat model. 2. BP was recorded with radiotelemetry devices and CO with ultrasonic transit-time probes. TPR was calculated from the BP and CO recordings. The contributions of endogenous ET and AVP were studied by infusing [d(CH(2))(5)(1),O-Me_Tyr(2),Arg(8)]-vasopressin, a V(1)-receptor antagonist, and bosentan, a mixed ET(A)/ET(B) receptor antagonist (Study 1). Vascular responsiveness was estimated from the changes in TPR evoked by i.v. infusions of ET-1 and AVP (Study 2). 3. In study 1, infusion of bosentan reduced TPR and BP dramatically in DOCA-salt hypertensive rats but not in SHAM control rats, and this effect was greater when the AVP system had been blocked. In contrast, the V(1) receptor antagonist alone failed to change TPR and BP in DOCA-salt hypertensive rats. However, subsequent infusion of the V(1) receptor antagonist during the plateau phase of the response in bosentan pretreated DOCA-salt hypertensive rats led to significant decreases in both BP and TPR. 4. In study 2, TPR and BP responses to ET-1, but not AVP, were greater in DOCA-salt rats than in control rats. CO responses to ET-1 or AVP were similar in the two groups. 5. The results suggest that both ET and AVP play a role in the maintenance of TPR and BP; when one system is blocked the other compensates. However, the magnitude of the contribution to the hypertensive state appears greater for ET than for AVP. Enhanced vascular responses to ET appear to contribute to this greater role.

Cardiovascular response of trained and untrained old men to mental challenge

The cardiovascular response to mental challenge of trained and untrained older men was examined. Blood pressure, heart rate, stroke volume, cardiac output, total peripheral resistance (TPR), rate pressure product, and cardiac contractility of 10 aerobically trained (trained) and 10 untrained (untrained) older men during and recovering from the Stroop task were compared. Fitness was assessed by online, open-circuit spirometry using a bicycle ergometer. Trained compared with untrained men showed significantly lower absolute heart rate during and recovering from the Stroop and greater left ventricular ejection time recovering from Stroop. Delta TPR scores were greater for Trained during and recovering from the Stroop, whereas delta systolic blood pressure was greater recovering from Stroop. These results indicate that although aerobically trained men possessed lower absolute heart rate their change in TPR and systolic blood pressure during mental challenge was significantly greater than that of untrained older men. The greater vascular response of the trained to mental challenge may reflect greater sensitivity to alpha-adrenergic stimulation.

Antihypertensive monotherapy and cardiovascular responses to an acoustic startle stimulus.

To determine contribution of the autonomic nervous system to cardiovascular reactivity to noise, acoustic startle stimulus (110 dB, 1-20 kHz, 0.150 s) was administered to 35 subjects (19 women, 16 men) with mild essential hypertension. Among these patients, 10 were unmedicated and 25 were receiving long-term monotherapy (10 were taking 100 mg atenolol, 5 were taking 10 mg prazosin, and 10 were taking 50 mg losartan daily). Polygraphic recordings were obtained in supine position. Blood pressure (BP) and heart rate (HR) levels were stable until the noise was administered. In the unmedicated group BP and HR were elevated during the first 10 s. BP returned to resting levels after this period. The calculated hemodynamic indexes showed a biphasic change in total peripheral resistance (TPR), with an overall vasoconstriction associated with the BP rise phase, preceding a delayed vasodilation. The lowest HR changes were observed in the beta-blocker group with increases of 6 beats/min and 3 beats/min after the first and second noise stimulations, compared with 10 beats/min and 5 beats/min in the unmedicated group. Prazosin significantly reduced the BP rises to 7 mm Hg and 6 mm Hg for systolic BP and diastolic BP after the first stimulation compared with 22 mm Hg and 17 mm Hg in the untreated group (p < 0.01). The second stimulation after prazosin determined -5 mm Hg and 1 mm Hg changes for systolic BP and diastolic BP respectively, compared to rises of 13 mmHg for systolic BP and 10 mmHg for diastolic BP in the untreated group (p < 0.01). The hemodynamic percentage changes resulting from the first stimulation indicated prazosin markedly reduced the noise-induced rise in TPR (p < 0.05). No effect of beta-blocker was detectable using percentage changes. The rises in BP were amplified in the losartan-treated subjects compared with the other groups. Because of a low resting TPR in this group, the percentage changes in TPR resulting from noise were amplified in the subjects treated with the AT1 receptor antagonist. In conclusion the acoustic startle stimulus appeared as a simple and reliable procedure for inducing transient increases due to a rise in TPR. Cardiovascular responses differed according to the antihypertensive monotherapy, with a limited effect of noise in the prazosin-treated group.

Shared and Simple Effects of Determinants of Mean Arterial Pressure During Handgrip and Mirror Tracing Tasks

Abstract Hierarchical linear regression (HLR) can be used to quantify the relative contribution specific cardiovascular (CV) mechanisms make to blood-pressure responses. The impact particular mechanisms exert varies depending on the nature of situational demands and the length of time these demands have been imposed. Theoretically, the determinants of blood-pressure changes may exercise their influence independently as simple effects, or they might evidence a relationship that is correlated or shared with other mechanisms. Following a procedure Lindenberger and Potter (1998) outlined, we used HLR and computations of shared versus simple effect ratios to quantify the portions of variance several cardiovascular parameters accounted for independently in mean arterial pressure (MAP) reactivity during isometric handgrip and mirror tracing. The predictor variables included heart rate (HR), total peripheral resistance (TPR), and cardiac output (CO). CV activity of 50 college-aged males was measured during adjacent 30-s periods using impedance cardiography and a Dinamap blood pressure monitor. HR reactivity predicted MAP changes during all measurement periods. However, for mirror tracing, a substantial portion of the variance in MAP accounted for by HR was shared with CO reactivity (39% for period 1; 13% for period 2). For handgrip, 5% and 20% of variance HR accounted for in MAP during periods 1 and 2, respectively, were shared with changes in TPR. CO shared trivial amounts of variance in MAP changes with HR during handgrip. Finally, CO changes were correlated with TPR changes and uncorrelated with MAP reactivity when handgrip was performed. However, adding CO to the equation improved TPR's predictive utility, suggesting that suppressor effects were present.

Short-term cardiovascular responses to rapid whole-body tilting during exercise.

Our objective was to characterize the responses of heart rate (HR) and arterial blood pressure (BP) to changes in posture during concomitant dynamic leg exercise. Ten men performed dynamic leg exercise at 50, 100, and 150 W and were rapidly and repeatedly tilted between supine (0 degrees ) and upright (80 degrees ) positions at 2-min intervals. Continuous recordings of BP and HR were made, and changes in central blood volume were estimated from transthoracic impedance. Short-lasting increases in BP were observed immediately upon tilting from the upright to the supine position (down-tilt), averaging +18 mmHg (50 W) to +31 mmHg (150 W), and there were equally short-lasting decreases in BP, ranging from -26 to -38 mmHg upon tilting from supine to upright (up-tilt). These components occurred for all pressure parameters (systolic, mean, diastolic, and pulse pressures). We propose that these transients reflect mainly tilt-induced changes in total peripheral resistance resulting from decreases and increases of the efficiency of the venous muscle pump. After 3-4 s (down-tilt) and 7-11 s (up-tilt) there were large HR transients in a direction opposite to the pressure transients. These HR transients were larger during the down-tilt (-15 to -26 beats. min(-1)) than during the up-tilt (+13 to +17 beats. min(-1)), and increased in amplitude with work intensity during the down-tilt. The tilt-induced HR fluctuations could be modelled as a basically linear function of an arterial baroreflex input from a site half-way between the heart and the carotid sinus, and with varying contributions of fast vagal and slow sympathetic HR responses resulting in attenuated tachycardic responses to hypotensive stimuli during exercise.

Estrogen restores role of basal nitric oxide in control of vascular tone in rats with chronic heart failure.

This study examined the cardiovascular effects of 17beta-estradiol in ovariectomized rats with heart failure. Two groups (50-60 days old) were implanted with 60-day-release pellets containing 17beta-estradiol (25 microg/day) or vehicle at 7 days before ligation of the left coronary artery. Another group was sham operated and given vehicle pellets. After 7 wk, they were studied under pentobarbital anesthesia. Relative to sham-operated rats, ligated rats had reduced mean arterial pressure (MAP, -24 +/- 6 mmHg), cardiac output (-27 +/- 4 ml/min), left ventricular (LV) end-systolic pressure (-29 +/- 8 mmHg), depressor responses to ACh (-6 +/- 4 mmHg at 7.2 microg/kg) and sodium nitroprusside (SNP, -22 +/- 6 mmHg at 9 microg/kg), and pressor responses to NG-nitro-L-arginine methyl ester (L-NAME, -14 +/- 6 mmHg at 8 mg/kg) and increased LV end-diastolic pressure (LVEDP, 10.3 +/- 0.8 mmHg) but no change in total peripheral resistance (TPR). Treatment of ligated rats with 17beta-estradiol reduced TPR (-0.19 +/- 0.06 mmHg . min . ml-1), LVEDP (-3.6 +/- 1 mmHg), and responses to ACh (-16 +/- 4 mmHg) and augmented responses to L-NAME (14 +/- 3 mmHg) but did not alter other variables. Therefore, 17beta-estradiol reduces preload and afterload and restores the vasodilator role of basal nitric oxide in ovariectomized rats with chronic heart failure.

Plasma catecholamines and haemodynamic changes during pneumoperitoneum.

Insufflation of CO2 into the abdomen is used during all kinds of laparoscopic operations. The procedure elicits haemodynamic and hormonal responses. The reports on sympathetic responses to laparoscopic surgery have been conflicting. However, few studies have assessed sympathetic and haemodynamic responses to CO2 insufflation per se, eliminating possible effects of intubation, skin incision, surgical manipulation and positioning of the body. No studies have measured both venous and arterial plasma catecholamines, the latter being a more sensitive indicator of sympathetic activity. In the present study, we hypothesised an increased sympathetic activity during pneumoperitoneum and an association between haemodynamic and sympathetic responses. Plasma adrenaline and noradrenaline from the radial artery and superior vena cava were measured immediately before and 10 min after abdominal insufflation of CO2 in 11 subjects. Haemodynamics were monitored invasively. During pneumoperitoneum arterial plasma noradrenaline increased from 155 (106, 209) pg/ml (median, lowest and highest quartile) to 283 (188, 378) pg/ml (P = 0.003), while there were no changes in arterial plasma adrenaline. The calculated arterial-superior vena cava difference in plasma noradrenaline did not change, indicating no increased sympathetic activity in the drainage area of the superior vena cava. Heart rate and cardiac index were unchanged, while total peripheral resistance and mean arterial blood pressure increased (P = 0.002). The changes in arterial plasma noradrenaline were closely related to the changes in total peripheral resistance (r = 0.69, P = 0.01). Plasma noradrenaline increases during pneumoperitoneum and is associated with changes in total peripheral resistance. Plasma adrenaline is unchanged and there is no evidence of increased sympathetic outflow to the drainage area of the superior vena cava. Thus, the increase in plasma noradrenaline may be due to more local activation of the sympathetic nervous system, probably somewhere from the drainage area of the inferior vena cava.

Stability of access resistance during haemodialysis.

Access blood flow (Qac) is considered a useful indicator in the surveillance of haemodialysis access function. However, changes in Qac may be due to changes in blood pressure and/or to changes in access resistance (AR). Weekly readings of Qac, cardiac output, and arterial blood pressure measured early and late during haemodialysis were obtained in 11 patients for a period of 3 weeks. Qac was determined from thermodilution of extracorporeal blood returning to the patient with reversed placement of blood lines and by measurement of arterial and venous blood temperatures in the extracorporeal circulation. Data are given as mean +/- SE. Qac dropped as mean arterial pressure (MAP) and total peripheral resistance (TPR) decreased, but increased when MAP and TPR increased. Linear regressions between the change in access flow and the change in MAP (deltaQac%=0.80*deltaMAP%-1.6, r2=0.39), and the change in TPR (deltaQac%= 0.54*deltaTPR%-9.2, r2=0.35) respectively, were significant (P<0.001). Whereas Qac significantly decreased (-8.4+/-3.3%, P<0.01) during the same treatment, AR remained unchanged (4.7+/-3.2%; P=NS). AR for all studies was 16.5+/-1.0 peripheral resistance units (1 PRU=2.226 kPa min l(-1)). There was a trend for resistance to increase (5.1+/-2.6%, P=NS) and for flow to decrease (-6.1+/-2.3%, P=NS) during the 3 weeks of the study. Qac measured during haemodialysis is variable and depends on haemodynamics, but AR is constant. AR is related to the physical structure of the peripheral access. Because of its intradialytic stability AR may be better suited as an indicator of access function.

Hemodynamic profile of corticotropin-induced hypertension in the rat.

To examine hemodynamic variables in corticotropin-induced hypertension in rats and the effects of reversal of the hypertension by L-arginine on the hemodynamic profile. Sixty male Sprague-Dawley rats were randomly divided into four groups: sham treatment (0.9% NaCl, injected subcutaneously); 0.5 mg/kg corticotropin per day, subcutaneously; 0.6% L-arginine in food plus sham; and L-arginine plus corticotropin. Systolic blood pressure, water and food intakes, urine volume, and body weight were measured every second day. After 10 days mean arterial blood pressure was measured by intra-arterial cannulation, and cardiac output, and renal, mesenteric, and hindquarter blood flows were determined using transonic small animal flowmeters. Injection of corticotropin increased blood pressure, water intake, urine volume, and plasma sodium concentration, and decreased body weight and plasma potassium concentration. It increased cardiac output (P < 0.01), mesenteric blood flow (P < 0.05), and renal vascular resistance (P < 0.05), and decreased renal blood flow (P < 0.05), but did not change calculated total peripheral resistance, hindquarter blood flow, mesenteric or hindquarter vascular resistance. L-arginine prevented corticotropin-induced rises in blood pressure (P < 0.001) and renal vascular resistance (P < 0.05), and a fall in renal blood flow (P < 0.05), but did not affect other hemodynamic variables. The hemodynamic profile of corticotropin-induced hypertension in the rat is characterized by a rise in cardiac output and renal vascular resistance, a fall in renal blood flow, but no change in total peripheral resistance, hindquarter blood flow, mesenteric vascular resistance, or hindquarter vascular resistance. L-arginine prevented corticotropin-induced rises both in blood pressure and in renal vascular resistance in the rat. These data suggest that the increase in renal vascular resistance might play a role in corticotropin-induced hypertension in the rat.

Effects of Nω-Nitro- l-Arginine and N-Acetyl- l-Cysteine on the Reversal of One-Kidney, One-Clip Hypertension

The present study evaluated whether nitric oxide (NO) synthesis blockade or potentiation (with N ω-nitro- l-arginine or N -acetyl- l-cysteine, respectively) modulates the systemic and renal responses to unclipping in anesthetized one-kidney, one-clip hypertensive rats (1K-1C). Cardiac output was measured by thermodilution. In time-control rats, mean arterial pressure (MAP) decreased from 197 ± 8 mm Hg to 139 ± 4 mm Hg 3 h after unclipping, and cardiac index (CI) decreased by 35%, with a transient rise in sodium and water excretion and no changes in total peripheral resistance (TPR), glomerular filtration rate (GFR), or renal plasma flow (RPF). Administration of N ω-nitro- l-arginine methyl ester (NAME, 10 μg/kg/min) blunted the hypotensive (from 190 ± 6 mm Hg to 157 ± 3 mm Hg), diuretic and natriuretic responses and potentiated the decrease in CI (40%) observed after unclipping, whereas TPR increased by 103%. Also, in rats given NAME, GFR and RPF decreased by 20% and 45%, respectively, at the end of the experiment. The effect of N -acetyl- l-cysteine (NAC, 300 mg/kg), a sulfhydryl group donor that may protect NO from free radical destruction by forming an S -nitrosothiol compound, was also evaluated. NAC potentiated the depressor response to unclipping (from 180 ± 5 mm Hg to 97 ± 3 mm Hg), and GFR and RPF increased by 80% and 35%, respectively. These effects of NAC appear to be NO dependent, as they were blocked by simultaneous administration of NAME. However, no significant differences were observed among groups in cumulative excretion of sodium and water, demonstrating that the hemodynamic effects of NAME and NAC after unclipping are due to mechanisms other than renal excretory changes. The results of the present study indicate that the cardiovascular depressor effects of unclipping are modulated by endothelium-derived nitric oxide.

Role of Physical Countermaneuvers in the Management of Orthostatic Hypotension: Efficacy and Biofeedback Augmentation

To evaluate the efficacy of various physical countermaneuvers in reducing orthostatic hypotension and its associated symptoms and to assess the efficacy of biofeedback training in enhancing the effectiveness of physical countermaneuvers. In nine study subjects with neurogenic orthostatic hypotension, four training sessions on physical countermaneuvers were performed after tilt-up, three with visual feedback on the effect of physical countermaneuvers on blood pressure and other cardiovascular variables. Blood pressure change and orthostatic symptoms during tilt-up were determined, as were the changes in total peripheral resistance, stroke index, and heart rate. The five female and four male patients had a mean age of 53 years and a mean duration of symptoms of 4.2 years. On an orthostatic symptom scale of 0 to 10, these patients had a mean symptom score of 7.3. The increment in systolic blood pressure was better for some maneuvers (such as leg crossing and a combination) than others (such as neck flexion and abdominal contraction). Three patterns of responses to biofeedback were found. Simple maneuvers such as squatting did not improve with training; visual feedback was needed for maneuvers such as thigh contraction, and performance declined without biofeedback; the third pattern, seen in maneuvers such as leg crossing, showed continued improvement with training, even without biofeedback. A survey at 3 to 4 months after training revealed continued use of physical maneuvers (3.8 +/- 3.1 per day), increased standing time with each episode of presyncopal symptoms (8.3 +/- 5.8 minutes), and continued global symptomatic improvement. Total peripheral resistance, but not heart rate or stroke index, showed significant regression with blood pressure improvement. Physical countermaneuvers are efficacious in reducing orthostatic hypotension, can be augmented by use of biofeedback, and may significantly improve the functional outcome. The major mechanism of improvement is an increase in total peripheral resistance, presumably by reducing the vascular capacitance.

Pharmacokinetic-haemodynamic relationships of 2-chloroadenosine at adenosine A1 and A2a receptors in vivo.

1. The purpose of the present study was to develop an experimental strategy for the quantification of the cardiovascular effects of non-selective adenosine receptor ligands at the adenosine A1 and A2a receptor in vivo. 2-Chloroadenosine (CADO) was used as a model compound. 2. Three groups of normotensive conscious rats received an short intravenous infusion of 1.4 mg kg-1 CADO during constant infusions of the A1-selective antagonist, 8-cyclopentyltheophylline (CPT; 20 micrograms min-1 kg-1), the A2a-selective antagonist, 8-(3-chlorostyryl) caffeine (CSC; 32 micrograms min-1 kg-1) or the vehicle. The heart rate (HR) and mean arterial blood pressure (MAP) were recorded continuously during the experiment and serial arterial blood samples were taken for analysis of drug concentrations. The ratio MAP/HR was also calculated, which may reflect changes in total peripheral resistance on the assumption that no changes in stroke volume occur. 3. During the infusion of CPT, CADO produced a reduction in both blood pressure and MAP/HR by activation of the A2a receptor. The concentration-effect relationships were described according to the sigmoidal Emax model, yielding potencies based on free drug concentrations (EC50,u) of 61 and 68 ng ml-1 (202 and 225 nM) for the reduction of blood pressure and MAP/HR, respectively. During the infusion of CSC, an EC50,u value of 41 ng ml-1 (136 nM) was observed for the A1 receptor-mediated reduction in heart rate. The in vivo potencies correlated with reported receptor affinities (Ki(A1) = 300 nM and Ki(A2a) = 80 nM). The maximal reductions in MAP/HR and heart rate were comparable to those of full agonists, with the Emax values of -12 +/- 1 x 10(-2) mmHg b.p.m.-1 and -205 b.p.m. respectively. 4. It is concluded that this integrated pharmacokinetic-pharmacodynamic approach can be used to obtain quantitative information on the potency and intrinsic activity of new non-selective adenosine receptor agonists at different receptor subtypes in vivo.

Coronary and total peripheral resistance changes during sleep in a porcine model.

Changes in autonomic tone in the vasculature during sleep may have important implications for silent ischemia and sudden cardiac death. Few models exist in which both cardiac output and coronary blood flow are continuously measured during natural sleep and autonomic mechanisms are assessed. Catheters were chronically implanted in the aorta to measure mean arterial pressure (MAP), and flow probes were placed on the ascending aorta and the circumflex coronary artery of 18 pigs. Electrodes determined sleep stage as either non-rapid eye movement (NREM) or rapid eye movement (REM) sleep. The MAP was 73 +/- 3 mmHg in the quiet awake state, did not change in NREM, and decreased to 64 +/- 2 mmHg in REM sleep (P < 0.05). In NREM sleep, heart rate did not change from awake state values of 136 +/- 8 beats/min but increased by 5 beats/min in REM sleep (P < 0.05). Coronary vascular resistance decreased from awake state values of 2.7 +/- 0.2 to 2.2 +/- 0.2 mmHg.ml-1.min in REM (P < 0.05); total peripheral resistance decreased from awake values of 0.061 +/- 0.004 mmHg.ml-1.min to 0.050 +/- 0.003 in REM sleep (P < 0.05). Those changes appear to have been mediated primarily by reduction of alpha-adrenergic activity. Spectral analysis of heart rate suggests that power in the high-frequency range (a presumed indicator of parasympathetic tone) was lower in REM sleep than NREM sleep.