Response To Cold Pressor Test Research Articles

Hemodynamic responses to the cold pressor test in individuals with metabolic syndrome: a case-control study in a multiracial sample of adults.

Previous research shows that exercise pressor and metaboreflex responses are significantly exaggerated in individuals with metabolic syndrome, but it is unclear if these exaggerated responses extend to the cold pressor test (CPT). This study tested the hypothesis that, contrary to previously reported exaggerated responses during exercise, CPT responses would not be significantly exaggerated in individuals with MetS compared to matched controls. Eleven individuals with MetS and eleven control participants matched by age, race, sex, and ethnicity completed a cardiometabolic prescreening and a CPT. Each CPT required participants to immerse their hand in ice water for two minutes while beat-by-beat blood pressure, heart rate (HR), and leg blood flow (LBF) were continuously measured. Leg vascular conductance (LVC) was calculated as LBF divided by mean arterial pressure (MAP). The precent changes in MAP, systolic blood pressure (SBP), diastolic blood pressure (DBP), HR, LBF, and LVC were compared across time (BL vs. Minutes 1 and 2 of CPT) and between groups (MetS vs. Control) using repeated measures analyses of variance. As expected, MAP (f = 32.11, p < 0.001), SBP (f = 23.18, p < 0.001), DBP (f = 40.39, p < 0.001), and HR (f = 31.81, p < 0.001) increased during the CPT, and LBF (f = 4.75, p = 0.014) and LVC (f = 13.88, p < 0.001) decreased. However, no significant main effects of group or group by time interactions were observed (f ≤ 0.391, p ≥ 0.539). These findings indicate that the hemodynamic responses to the CPT are not significantly exaggerated in MetS, and therefore, previous reports of exaggerated exercise pressor and metaboreflex responses in MetS cannot be attributed to generalized sympathetic overexcitability.

Sex Differences in Vascular Reactivity with Acute and Chronic Hypoxia

Objective Males and females may respond differently to hypoxic exposure at high altitude. Females have reduced vascular resistance in response to hypoxia, possibly due to differences in adrenergic control. We investigated the role of sex in vascular control during hypoxia. We hypothesized females have reduced vasoreactivity to sympathetic stressors compared to males during acute and prolonged hypoxia exposure. Methods We studied a convenient sample of 7 males and 6 females at three time points: 1) low altitude (Calgary AB, 1100m) breathing room air (normoxia; LOW) and acute isocapnic hypoxia (PETO2~50mmHg; PETCO2~32mmHg; ACUTE); 2) during early (day 2-3; EARLY) and 3) late (day 8-10; LATE) acclimatization at high altitude (White Mountain, CA; 3800m) breathing room air (PETO2~50mmHg) and hyperoxia (100% O2). Heart rate (HR), mean arterial pressure (MAP), and blood oxygen saturation (SpO2) were collected beat-by-beat. Participants performed a cold pressor test (CPT) to assess integrated cardiovascular reactivity to a sympathetic stressor. To isolate α1-adrenergic receptor sensitivity, we delivered a graded series of phenylephrine hydrochloride (PE) injections. Statistical analysis included a mixed model ANOVA, and Holm-Sidak post hoc tests when we identified main effects (α<0.05). Results In response to CPT, peak change in MAP decreased with hypoxia duration (p<0.001). There was also a significant interaction between condition and sex (p=0.038). While LOW (+17.0±5.9mmHg) and ACUTE (+15.3±4.7mmHg) responses were not different (p=0.565), males showed a marked decrease in peak MAP response to CPT at EARLY (+10.2±4.9mmHg) and LATE (+9.8±5.4mmHg) compared to LOW (both p<0.001). Similarly, LOW (+11.8±8.4mmHg) and ACUTE (+8.2±3.8mmHg) peak MAP responses to CPT were not different in females (p=0.137). Though female responses decreased between LOW and EARLY (+6.3±3.3mmHg; p=0.042), they returned to similar values by LATE (+9.7±7.5mmHg; p=0.479). Adrenergic sensitivity slope was decreased at altitude (p=0.025) independent of sex (p=0.977). LOW (0.33±0.21) and ACUTE (0.22±0.10) sensitivity were not different (p=0.309). Notably, sensitivity was reduced at altitude at LATE (0.14±0.16; p=0.043), but not significantly at EARLY (0.16±0.18; p=0.051) compared to LOW. Hyperoxia did not correct CPT responses or PE adrenergic sensitivity to low altitude values at EARLY (p<0.001; p=0.01, respectively) nor LATE (p=0.013; p=0.042, respectively). Conclusions Our data indicate decreased α1-adrenergic responsiveness with acclimatization underlies blunted vascular reactivity in both sexes. However, female responses to CPT returned to low altitude values following 8 days at altitude, indicating differential adaptation. Additional mechanisms influencing the vascular response to stress (e.g. less neuropeptide mediated constriction, higher β-adrenergic dilation) may account for lower responsiveness in females compared to males. Our results have implications for understanding vascular function at high altitude and in clinical conditions characterized by hypoxemia.

Cold pressor test in spinal cord injury-revisited.

Systematic review. A spinal cord injury (SCI) commonly results in alterations of cardiovascular physiology. In order to investigate such alterations, the cold pressor test (CPT) has been used as an established challenge test. This review summarizes the basic physiology underlying a CPT, discusses potential mechanisms responsible for abnormal pressor responses following SCI, and highlights the utility of CPT in the SCI population. Canada and Switzerland. We have completed a comprehensive review of studies that have investigated the effect of foot or hand CPT on hemodynamic indices in individuals with SCI. Depending on the level of spinal cord lesion and the location of cold application, i.e., above or below the lesion, mean arterial pressure typically increases (ranging between 4 and 23 mmHg), while heart rate responses demonstrated either a decrease or an increase (ranging between -4 and 24 bpm) during CPT. The increase in blood pressure during foot CPT in high-level lesions might not necessarily be attributed to a physiological CPT response as seen in able-bodied individuals, but rather due to a reflexic sympathetic discharge below the level of lesion, known as autonomic dysreflexia. Further investigations in a wider range of individuals with SCI including incomplete injuries might be helpful to examine the ability of CPT assessing the integrity of the autonomic nervous system following SCI. Furthermore, additional autonomic tests are needed to emphasize the integrity of autonomic pathways and to account for the complexity of the autonomic nervous system.

(241) Effects of demographics and water temperature on cold pressor test responses in patients with opioid use disorder

(241) Effects of demographics and water temperature on cold pressor test responses in patients with opioid use disorder

Effect of Cold Stress and the Cold Pressor Test on Blood Pressure and Heart Rate

Background: Temperature and other environmental stressors are known to affect blood pressure and heart rate. The cold pressor test is used clinically to evaluate autonomic and left ventricular functions. Aims: This project was done to test the hypothesis that blood pressure and heart rate is altered during the cold pressor test. Methods: Students performed the cold pressor test, to study the change in blood pressure following an environmental stress. 40 medical students from the Ist year MBBS batches were selected and tested for cold pressor test during 1 to 2 min immersion of one hand in ice water. This test used cold as a stressful stimulus. The response of the subject was measured by the change in blood pressure and heart rate after the application of cold stimulus. Results: The study showed that the correlation between Anxiety state scores and cold pressor test response was not significant statistically. The correlation between Anxiety trait scores and cold pressor test response was also not significant statistically. Conclusion: The results indicate that the blood pressure and heart rate increases following an environmental stress. This activity can be easily adapted and students can learn about the test and carry out the test on their classmates.

Comprehensive assessment of impaired peripheral and coronary artery endothelial functions in smokers using brachial artery ultrasound and oxygen-15-labeled water PET

BackgroundComprehensive evaluation of endothelium-dependent and endothelium-independent vascular functions in peripheral arteries and coronary arteries in smokers has never been performed previously. Through the use of brachial artery ultrasound and oxygen-15-labeled water positron emission tomography (PET), we sought to investigate peripheral and coronary vascular dysfunctions in smokers. Methods and resultsEight smokers and 10 healthy individuals underwent brachial artery ultrasound at rest, during reactive hyperemia [250mmHg cuff occlusion (flow-mediated dilatation (FMD)], and following sublingual nitroglycerin (NTG) administration. Myocardial blood flow (MBF) was assessed through O-15-labeled water PET at rest, during adenosine triphosphate (ATP) administration, and during a cold pressor test (CPT). Through ultrasound, smokers were shown to have significantly reduced %FMD compared to controls (6.62±2.28% vs. 11.29±2.75%, p=0.0014). As assessed by O-15-labeled water PET, smokers were shown to have a significantly lower CPT response than were controls (21.1±9.5% vs. 50.9±16.9%, p=0.0004). There was no relationship between %FMD and CPT response (r=0.40, p=0.097). Endothelium-independent vascular dilatation was similar for both groups in terms of coronary flow reserve with PET (p=0.19). Smokers tended to have lower %NTG in the brachial artery (p=0.055). ConclusionsSmokers exhibited impaired coronary endothelial function as well as peripheral brachial artery endothelial function. In addition, there was no correlation between PET and ultrasound measurements, possibly implying that while smokers may have systemic vascular endothelial dysfunction, the characteristics of that dysfunction may be different in peripheral arteries and coronary arteries.

Augmented pressor and sympathetic responses to skeletal muscle metaboreflex activation in type 2 diabetes patients.

Previous studies have reported exaggerated increases in arterial blood pressure during exercise in type 2 diabetes (T2D) patients. However, little is known regarding the underlying neural mechanism(s) involved. We hypothesized that T2D patients would exhibit an augmented muscle metaboreflex activation and this contributes to greater pressor and sympathetic responses during exercise. Mean arterial pressure (MAP), heart rate (HR), and muscle sympathetic nerve activity (MSNA) were measured in 16 patients with T2D (8 normotensive and 8 hypertensive) and 10 healthy controls. Graded isolation of the muscle metaboreflex was achieved by postexercise ischemia (PEI) following static handgrip performed at 30% and 40% maximal voluntary contraction (MVC). A cold pressor test (CPT) was also performed as a generalized sympathoexcitatory stimulus. Increases in MAP and MSNA during 30 and 40% MVC handgrip were augmented in T2D patients compared with controls (P < 0.05), and these differences were maintained during PEI (MAP: 30% MVC PEI: T2D, Δ16 ± 2 mmHg vs. controls, Δ8 ± 1 mmHg; 40% MVC PEI: T2D, Δ26 ± 3 mmHg vs. controls, Δ16 ± 2 mmHg, both P < 0.05). MAP and MSNA responses to handgrip and PEI were not different between normotensive and hypertensive T2D patients (P > 0.05). Interestingly, MSNA responses were also greater in T2D patients compared with controls during the CPT (P < 0.05). Collectively, these findings indicate that muscle metaboreflex activation is augmented in T2D patients and this contributes, in part, to augmented pressor and sympathetic responses to exercise in this patient group. Greater CPT responses suggest that a heightened central sympathetic reactivity may be involved.

P-38 * NO INFLUENCE OF OPIOID RECEPTOR, MU 1 (OPRM1) GENE POLYMORPHISMS ON PAIN SENSITIVITY AMONG OPIOID DEPENDENT PATIENTS ON METHADONE MAINTENANCE THERAPY (MMT) IN MALAYSIA

Heightened pain sensitivity was frequently reported in opioid dependent patients on methadone maintenance therapy (MMT). This study investigated the influence of OPRM1 polymorphisms on pain sensitivity. Subjects were 148 Malay male opioid dependent patients receiving MMT. Their pain threshold (time elapsed when the subject started to perceive pain after immersion of hand), tolerance (time required for hand withdrawal), and intensity (0 - 100 visual analogue scale (VAS)) in response to cold pressor test (CPT) were measured at 0 hour (i.e. the time of the first CPT, and at 2, 4, 8, 12, and 24 hours after that. DNA was extracted from blood and subjected to PCR-genotyping. The differences of CPT responses between the OPRM1 polymorphisms were analysed using repeated measure analysis of variance (RM-ANOVA). There were no significant differences of pain responses (pain threshold, tolerance and intensity) between 118A > G and IVS2 + 691G > C polymorphisms of OPRM1 among opioid depedent subjects using genotype and allelic additive model, genotype dominant and recessive model, haplotypes and diplotypes analysis. The results suggest that the OPRM1 polymorphisms were not associated with differences in pain sensitivity. However, further investigations in larger numbers, other populations and pain models are required to confirm these findings.

Vasoreactivity before and after handgrip training in chronic heart failure patients

The purpose of this study was to investigate the vasodilatory and vasoconstrictor responses of the brachial artery in patients with chronic heart failure (CHF) and controls (CON) before and after a period of training and detraining. MethodsCHF (n = 10; age = 62 ± 8 yrs) and CON (n = 10; age = 55 ± 5 yrs) subjects completed 4 weeks of bilateral handgrip training (20 min; 60% of maximal handgrip strength; 15 grips*min−1; 4 days*week−1). Handgrip strength was measured using a hand dynamometer. Brachial artery flow-mediated dilation (BAFMD) and cold pressor test (CPT) responses were determined using ultrasonography prior to training, at the end of 4 weeks of training and following 4 weeks of detraining. Absolute (mm) BAFMD and CPT responses were combined to yield a vascular operating range (VOR). ResultsBaseline BAFMD was higher in CON (CHF: 2.98 ± 1.49%; CON: 6.21 ± 1.21%; p = 0.01), while CPT responses were higher in CHF (CHF: 3.38 ± 0.83%; CON: 2.46 ± 0.62%; p = 0.05). Baseline VOR tended to be greater in the CON subjects (CHF: 0.28 ± 0.05 mm; CON: 0.32 ± 0.12 mm; p = 0.06). Training increased handgrip strength (∼5%; p < 0.05, for both groups), BAFMD (CHF: 2.98 ± 1.49% to 3.75 ± 1.56%; CON: 6.21 ± 1.21% – 8.02 ± 1.75%; p = 0.01) and VOR (CHF: 0.28 ± 0.05 mm – 0.3 ± 0.09 mm; CON: 0.32 ± 0.12 mm – 0.42 ± 0.11 mm; p = 0.01). There were no significant changes in CPT responses. All markers approached pre-training values following detraining. ConclusionHandgrip exercise increases strength, BAFMD and VOR in both CHF and CON subjects. These improvements are transient and return to pre-training values after removal of the training stimulus.

Comparison of laser speckle contrast imaging with laser Doppler for assessing microvascular function

ObjectiveTo compare the inter-day reproducibility of post-occlusive reactive hyperaemia (PORH) and sympathetic vasomotor reflexes assessed by single-point laser Doppler flowmetry (SP-LDF), integrating-probe LDF (IP-LDF) and laser speckle contrast imaging (LSCI), and the spatial variability of PORH assessed by IP-LDF and LSCI. We also evaluated the relationship between IP-LDF and LSCI perfusion values across a broad range of skin blood flows. MethodsEighteen healthy adults (50% male, age 27±4years) participated in this study. Using SP-LDF, IP-LDF and LSCI, indices of skin blood flow were measured on the forearm during PORH (1-, 5- and 10-min occlusions) and on the finger pad during inspiratory gasp and cold pressor tests. These tests were repeated 3–7days later. Data were converted to cutaneous vascular conductance (CVC; laser Doppler flow/mean arterial pressure) and expressed as absolute and relative changes from pre-stimulus CVC (ΔCVCABS and ΔCVCREL, respectively), as well as normalised to peak CVC for the PORH tests. Reproducibility was expressed as within-subjects coefficients of variation (CV, in %) and intraclass correlation coefficients. ResultsThe reproducibility of PORH on the forearm was poorer when assessed with SP-LDF and IP-LDF compared to LSCI (e.g., CV for 5-min PORH ΔCVCABS=35%, 27% and 19%, respectively), with no superior method of data expression. In contrast, the reproducibility of the inspiratory gasp and cold pressor test responses on the finger pad were better with SP-LDF and IP-LDF compared to LSCI (e.g., CV for inspiratory gasp ΔCVCREL=13%, 7% and 19%, respectively). The spatial variability of PORH responses was poorer with IP-LDF compared to LSCI (e.g., CV ranging 11–35% versus 3–16%, respectively). The association between simultaneous LSCI and IP-LDF perfusion values was non-linear. ConclusionThe reproducibility of cutaneous PORH was better when assessed with LSCI compared to SP-LDF and IP-LDF; probably due to measuring larger skin areas (lower inter-site variability). However, when measuring sympathetic vasomotor reflexes on the finger pad, reproducibility was better with SP-LDF and IP-LDF, perhaps due to the high sensitivity of LSCI to changes in skin blood flow at low levels.

Sex differences in the modulation of vasomotor sympathetic outflow during static handgrip exercise in healthy young humans

Sex differences in sympathetic neural control during static exercise in humans are few and the findings are inconsistent. We hypothesized women would have an attenuated vasomotor sympathetic response to static exercise, which would be further reduced during the high sex hormone [midluteal (ML)] vs. the low hormone phase [early follicular (EF)]. We measured heart rate (HR), blood pressure (BP), and muscle sympathetic nerve activity (MSNA) in 11 women and 10 men during a cold pressor test (CPT) and static handgrip to fatigue with 2 min of postexercise circulatory arrest (PECA). HR increased during handgrip, reached its peak at fatigue, and was comparable between sexes. BP increased during handgrip and PECA where men had larger increases from baseline. Mean ± SD MSNA burst frequency (BF) during handgrip and PECA was lower in women (EF, P < 0.05), as was ΔMSNA-BF smaller (main effect, both P < 0.01). ΔTotal activity was higher in men at fatigue (EF: 632 ± 418 vs. ML: 598 ± 342 vs. men: 1,025 ± 416 a.u./min, P < 0.001 for EF and ML vs. men) and during PECA (EF: 354 ± 321 vs. ML: 341 ± 199 vs. men: 599 ± 327 a.u./min, P < 0.05 for EF and ML vs. men). During CPT, HR and MSNA responses were similar between sexes and hormone phases, confirming that central integration and the sympathetic efferent pathway was comparable between the sexes and across hormone phases. Women demonstrated a blunted metaboreflex, unaffected by sex hormones, which may be due to differences in muscle mass or fiber type and, therefore, metabolic stimulation of group IV afferents.

Genetic correlation of blood pressure responses to dietary sodium and potassium intervention and cold pressor test in chinese population

We examined the genetic association between blood pressure (BP) responses to dietary sodium and potassium intervention and to cold pressor test (CPT) in a large family-based dietary feeding study. The dietary intervention and CPT were conducted among 1906 participants in rural China. The dietary intervention included three 7-day periods of low-sodium feeding (51.3 mmol per day), high-sodium feeding (307.8 mmol per day) and high-sodium feeding plus potassium supplementation (60 mmol per day). BP responses to high-sodium intervention had strong genetic correlations (ρ(G)) with both BP responses to low sodium (ρ(G)=-0.43 to -0.54, P-values=0.0005 to 0.03) and to potassium supplementation (ρ(G)=-0.41 to -0.49, P-values=0.001 to 0.005) interventions. Most environmental correlations between BP responses to various dietary interventions were significant. The ρ(G) between BP responses to CPT and to high-sodium intervention and potassium supplementation were statistically significant. For example, the ρ(G) between maximum BP responses to CPT and BP responses to high-sodium intervention was 0.37 (P=0.006) for systolic BP (SBP) and 0.41 (P=0.002) for diastolic BP (DBP). The ρ(G) between maximum BP responses to CPT and BP responses to potassium intervention was -0.42 (P=0.001) for SBP and -0.46 (P=0.001) for SBP. Our study suggests that there are common genetic determinants that influence BP responses to dietary sodium and potassium interventions and to CPT.

Quantitative analysis of coronary endothelial function with generator-produced 82Rb PET: comparison with 15O-labelled water PET

Endothelial dysfunction is the earliest abnormality in the development of coronary atherosclerosis. 82Rb is a generator-produced positron emission tomography (PET) myocardial perfusion tracer that is becoming more widely used. We aimed to (1) develop a method for quantitative assessment of coronary endothelial function using the myocardial blood flow (MBF) response during a cold pressor test (CPT) in smokers, measured using 82Rb PET, and (2) compare the results with those measured using 15O-water PET. MBF was assessed at rest and during the CPT with 82Rb and 15O-water in nine controls and ten smokers. A one-compartment model with tracer extraction correction was used to estimate MBF with both tracers. CPT response was calculated as the ratio of MBF during the CPT to MBF at rest. At rest, measurements of MBF for smokers vs controls were not different using 15O-water (0.86±0.18 vs 0.70±0.13, p=0.426) than they were using 82Rb (0.83±0.23 vs 0.62±0.20, p=0.051). Both methods showed a reduced CPT response in smokers vs controls (15O-water, 1.03±0.21 vs 1.42±0.29, p=0.006; 82Rb, 1.02±0.28 vs 1.70±0.52, p<0.001). There was high reliability [intraclass correlation coefficients: 0.48 (0.07, 0.75)] of MBF measurement between 82Rb and 15O-water during the CPT. Using a CPT, 82Rb MBF measurements detected coronary endothelial dysfunctions in smokers. 82Rb MBF measurements were comparable to those made using the 15O-water approach. Thus, 82Rb PET may be applicable for risk assessments or evaluation of risk factor modification in subjects with coronary risk factors.

About 7–day (circaseptan) and circadian changes in cold pressor test (CPT)

We assess circadian (CD) and circaseptan (CS) changes in the blood pressure (BP) response to a 1–min immersion of the hand into ice water, the cold pressor test (CPT). An about 8 mmHg BP increase in the CPT reported by others for health and an elevation >25 mmHg for patients with “hypertension” have been viewed as predisease, but variables related to the vascular system exhibit prominent CD, CS and circannuals, among other components of their genetically anchored time structure or chronome, and may also have to be considered. Hence, a 16-year-old adolescent (ML) immersed her hand into ice water every 2–4 h for 2 days and once daily in the morning thereafter for 1 week ( N = 25), as did, only for <2 days (≥24 h), four adults 20–66 years of age. BP and heart rate (HR) were monitored automatically around the clock at 15–min intervals and at 1–min intervals before and immediately after the CPT. Data were analyzed by cosinor. The difference between the first post-CPT BP value and the mean of the last seven values prior to the CPT was a measure of CPT response (at 1–min). Overall, ML’s systolic (S) BP increased by 8.2 ± 1.4 mmHg and her diastolic (D) BP by 6.2 ± 0.9 mmHg ( P < 0.001). Increases were found in 96% of the tests for SBP, 92% for DBP and 20% for HR. There was only one tie for HR (4%), resulting in a HR decrease in 76% of CPTs. The BP response to CPT at 1 min was CS-dependent. The CS double amplitudes are 12.5 ± 4.1 for SBP ( P = 0.019) and 7.8 ± 2.8 mmHg for DBP ( P = 0.030), with acrophases occurring on late Sunday, early Monday (at –50° and –67° from 00:00 h from Saturday to Sunday for SBP and DBP, respectively, with 360° ≡ 1 week). The response of HR did not allow the detection of a CS rhythm ( P = 0.969). The CD response peaked in the early morning hours; with 24 h ≡ 360° and 0° = local midnight, the acrophase ( φ) for SBP is at –80° and for DBP at –113°, in keeping with earlier results from four adult subjects (SBP: –37°; DBP: –42°), individual differences notwithstanding. The average timing of the largest overall response of BP to CPT coincides with the timing of the response to other stimuli. The CS acrophases coincide with the times of increased morbidity/mortality from vascular diseases. Chronomes, time structures broader than circadian, notably their about-weekly components, should be considered, not only at the extremes of life when the CS and about-half-weekly rhythms are particularly prominent in BP and HR but also in interpreting BP responses as a gauge of vascular disease status in adolescents.

Effect of oral nitroglycerin and cold stress on myocardial perfusion in areas subtended by stenosed and nonstenosed coronary arteries

Physical obstruction and coronary vasoconstriction mediated by adrenergic stress are believed to be responsible for episodes of myocardial hypoperfusion and angina. Nitroglycerin relieves symptoms by reducing preload and dilating epicardial vessels. The net perfusion change and relation to stenosis severity of nitroglycerin and adrenergic stress have been debated. This study aimed to evaluate whether oral nitroglycerin and adrenergic stress alters perfusion in myocardial segments subtended by stenosed and nonstenosed coronary arteries. Myocardial perfusion was quantified (using N-13-ammonia positron emission tomography [PET]) at rest, after oral nitroglycerin 400 μg, and after cold stress in 25 patients with coronary artery disease (62 ± 9 years, 21 men) and in 30 controls (34 ± 9 years, 22 men). Myocardial perfusion was quantified in areas supplied by stenosed (>70%) and nonstenosed (<30%) coronary arteries. The cold pressor test did not significantly alter myocardial perfusion in any of the groups. However, when normalized for rate-pressure product, the response in stenosed areas showed a significantly more pronounced reduction compared with nonstenosed areas (0.78 ± 0.18 vs 0.64 ± 0.19 ml/g/min, p <0.005 and 0.86 ± 0.19 vs 0.73 ± 0.24 ml/g/min, p <0.05, p <0.05) for intergroup comparison. In both stenosed areas and nonstenosed areas nitroglycerin increased perfusion (0.51 ± 0.14 vs 0.60 ± 0.17 ml/g/min, p <0.05 and 0.56 ± 0.14 vs 0.61 ± 0.17 ml/g/min, p <0.05). Nitroglycerin did not alter myocardial perfusion in the control group. There was a negative correlation between the cold pressor test response and stenosis severity (r 2 = 0.17, p <0.046), whereas this was not the case for nitroglycerin. In patients with coronary artery disease, myocardial segments supplied by stenosed coronary arteries showed an altered perfusion response to adrenergic stress. Oral nitroglycerin increased myocardial perfusion irrespective of the presence of a stenosis.

Subtle involvement of the sympathetic nervous system in amyotrophic lateral sclerosis.

The literature on the involvement of the autonomic nervous system (ANS) in amyotrophic lateral sclerosis (ALS) is conflicting. We therefore investigated several aspects of autonomic function, namely muscle sympathetic nerve activity (MSNA), blood pressure, cardiac function (electrocardiogram; ECG), and respiration in 16 patients with sporadic ALS and in 12 age-matched healthy volunteers, both at rest and during sympathoexcitatory stimulation. We measured MSNA by provoking venous pooling during short-lasting lower body negative pressure (LBNP) and during the cold pressor test (CPT). To assess the vagal (baroreflex) control of heart rate (HR), we measured spontaneous baroreflex sensitivity (BRS). To assess the involvement of the ANS beyond the cardiovascular system, we measured the sympathetic skin response (SSR). The stand-up test showed that none of the subjects had orthostatic intolerance. In comparison with the control group, the ALS patients had an increased HR and a decreased BRS at rest, and a reduced MSNA response to LBNP. The CPT response was normal and the total MSNA at rest did not differ significantly from that of controls. The latencies of the palmar and plantar SSR were prolonged, and in 3 ALS patients there was no plantar SSR. The results indicate that the sympathetic nervous system shows subtle abnormalities in ALS, predominantly sympathetic overactivity. They also point to the involvement of the preganglionic sympathetic column as the cause of the higher sympathetic activity and the absence of SSR. The higher sympathetic activity is postulated to be due to changes in modulation of the sympathetic system, whereas the absence of the SSR is probably caused by disruption of the reflex pathway.

Hereditary intermediate phenotypes in African American hypertension.

Essential hypertension is a heterogeneous and multifactorial disorder and is at least twice as frequent among African Americans as in the general population. Inheritance of high blood pressure is complex, with the gene(s) responsible for hypertension still remaining elusive. A useful strategy for investigating the heritability of hypertension is to evaluate 'intermediate phenotypes'--simple Mendelian or monogenic traits that are associated with hypertension. These intermediate steps may identify potential pathophysiological factors that antedate the development of high blood pressure and suggest candidate genes. We are attempting to identify and characterize several such intermediate phenotypes, in particular as these might apply to hypertension in African Americans. We studied several physiological and biochemical candidate intermediate phenotypes in untreated black and white patients with essential hypertension and in their normotensive counterparts stratified by genetic risk of hypertension. Promising intermediate phenotypes, which may be useful for studies in African American families, include baroreceptor sensitivity to low and high pressure stimuli, cold pressor test responses, and biochemical markers such as plasma chromogranin A, dopamine-beta-hydroxylase and urinary kallikrein excretion. Identification of genes involved in complex traits such as hypertension may be facilitated by the intermediate phenotype approach, combined with recent advances in quantitative genetics and linkage mapping. Further studies are needed to pinpoint the nature of genes in African American hypertension.

Cold Pressor Test as a Predictor of the Severity of Hypertension

This report examines the cold pressor test (CPT) as it relates to the severity of hypertension. A total of 123 hypertensive patients were studied by physical examination, retinal funduscopy, chest roentgenogram, electrocardiogram, blood urea nitrogen measurement, and urinalysis. Causal and valid basal resting blood pressure determinations were made, followed by immersion of one hand in ice water for 2 minutes. All 21 patients with arteriosclerotic, 78 with essential, and 24 with renal hypertension had hyperreactive responses to the CPT (> 20/20 mm Hg) as compared with the normotensive subjects. The CPT-induced increase in diastolic pressure was significantly higher in hypertensives with left ventricular hypertrophy (LVH). CPT responses were also greater in hypertensives with higher degrees of retinopathy. These findings indicate that the diastolic rise on cold pressor testing can be used as a measure of severity of hypertension, especially in the presence of LVH and severe retinopathy. The CPT is inexpensive and noninvasive and can aid the clinician in managing the hypertensive patient. The CPT may also be useful as a predictor of complications of hypertension in selected individuals.

916-90 Is Baroreflex Failure Different from Idiopathic Baroreceptor Dysfunction?

Baroreflex failure (BRF) due to local causes was reported as a syndrome of labile hypertension, exaggerated response to cold pressor test (CPT) and elevated plasma catecholamines. We hypothesized that the pattern of autonomic abnormalities is different in the idiopathic type of BR dysfunction (BRD). Twenty four subjects (13 M: 11 F; age 62 ± 16 yrs.) with tilt-induced orthostatic hypotension (OH) were tested for: Valsalva, CPT, baroreflex sensitivity (heart rate response to acute BP alteration using Phenylephrine [PE] and amylnitrite inhalation [ANI]. BRD was diagnosed by blocked Valsalva, abnormal PE and/or AN. Two groups were defined by the results of BR and tilt; 19 with BRD (OH-BRD) and 5 with normal BR (OH-NBR). They were compared to results in 31 control subjects (19 M: 12 F; age 40 ± 15 yrs.) who had normal tilt and normal BR (N-NBR). Plasma Norepinephrine (NE) was determined in supine and tilt positions. Tilt Δ(SBP) CPT Δ(SBP) AN (Slope) PE (Slope) Tilt (ΔNE) 1. OH-BRD -63 ± 21 * 22 ± 9 * 0.0 ± 06 *† 0.4 ± 1 † 15.4 ± 21.6 2.0H-NBR -36 ± 11 ‡ 34 ± 10 3.8 ± 24 8.8 ± 3 28.4 ± 17.0 3. NL-NBR -6 ± 8 29 ± 15 4.2 ± 29 7.5 ± 7 24.6 ± 18.9 X ± SD, P &lt; 0.017 * 1 vs 3 † vs 2 ‡ 2vs 3 (1) Patients with idiopathic BRD present with OH, have attenuated response to CPT and normal catecholamine response to tilt. (2) OH-BRD and BRF are two different syndromes with different etiologies and clinical manifestations; however, both have BR abnormalities.

Effects of atropine on adrenergic responsiveness and reflex vasoconstriction in humans.

To determine whether cholinergic mechanisms contribute to blood pressure regulation, we examined the effects of atropine on pressor responses to phenylephrine and vasoconstrictor responses to the cold pressor test (CPT) and lower body negative pressure (LBNP) in 16 healthy subjects. Heart rate, blood pressure and cardiac index were significantly increased, and central venous pressure (CVP) was significantly decreased after atropine (0.04mg/kg). After atropine, pressor responses to phenylephrine at doses of 20, 40 and 80 micrograms were significantly increased by 101, 112 and 93% (p less than 0.001); however, atropine attenuated pressor responses to CPT (p less than 0.001) and forearm vasoconstrictor responses to LBNP. In 6 propranolol-treated subjects, atropine also augmented pressor responses to phenylephrine but attenuated pressor responses to CPT. These results suggest that atropine augments the pressor response to an alpha-agonist, which may be partly explained by inhibition of compensatory vascular responses mediated by cholinergic mechanisms.