Increased α‐Adrenergic responsiveness in idiopathic raynaud's disease

Freedman, Robert R.; Sabharwal, S. C.; Desai, Nagaraj; Wenig, Paul; Mayes, Maureen D.

doi:10.1002/anr.1780320110

Cited by 69 publications

(22 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As far as the responses in the contralateral hand are concerned, our results are consistent with reports that the reflex vasoconstrictor response evoked in the finger by rapid cooling of the neck was similar in controls and in subjects with primary Raynaud's disease [10], and with evidence that the reflex increases in sympathetic outflow to the cutaneous vasculature of one hand that were evoked by cooling of the contralateral hand were similar in the two groups of Primary Raynaud's disease, cool stimuli and endothelin subjects [11]. Further, considering the cooled hand, there is no reason to argue, from the magnitude of the responses, that the direct effect of cooling on the cutaneous circulation was greater in the subjects with primary Raynaud's disease.…”

Section: Discussionsupporting

confidence: 92%

Cardiovascular responses evoked by mild cool stimuli in primary Raynaud's disease: the role of endothelin

1999

View full text Add to dashboard Cite

In control subjects and in subjects with primary Raynaud's disease, sudden sound evokes the pattern of the alerting response, which includes cutaneous vasoconstriction and vasodilatation in forearm muscle. However, whereas this pattern of response habituates on repetition of the sound stimulus in control subjects, both cutaneous vasoconstriction and muscle dilatation persist in subjects with primary Raynaud's disease. The aim of the present study was to test whether a similar disparity exists between control subjects and those with primary Raynaud's disease for the response to mild cool stimuli, and whether the cutaneous response is accompanied by the release of endothelin-1 (ET-1). In nine subjects with primary Raynaud's disease and in nine matched controls, the left hand was placed in cool water at 16 degrees C for 2 min five times on each of three experimental sessions on days 1, 3 and 5, with blood being taken from the venous drainage of the cooled hand before and at the end of the second session. In response to the first cool stimulus in Session 1, the subjects with primary Raynaud's disease showed a decrease in digital cutaneous vascular conductance (DCVC) in both the right and left hands, as indicated by a laser Doppler recording of erythrocyte (red cell) flux divided by arterial pressure, and six of the nine subjects showed an increase in forearm vascular conductance (FVC), as indicated by forearm blood flow measured by plethysmography divided by arterial pressure. On repetition of the stimulus in Session 1, there was no change in the magnitude of the increase in FVC, but the evoked decreases in DCVC became more prolonged in both the right and the left hand. Similar responses occurred in Sessions 2 and 3; in Session 2, the ET-1 concentration increased from a baseline value of 2.15+/-0.26 fM to 2.72+/-0.37 fM after five stimuli. There was no habituation of the increase in FVC over Sessions 1, 2 and 3, judging from the mean changes in each session. Control subjects also showed a decrease in DCVC in both hands, and in eight out of nine subjects there was an increase in FVC in response to the first cool stimulus in Session 1. However, on repetition of the stimulus in Session 1, the increase in FVC habituated, while there was no prolongation of the decrease in DCVC; in addition, the ET-1 concentration did not change in Session 2 in response to the stimulus (2.07+/-0.28 compared with 2.29+/-0.30 fM). Further, the increase in FVC habituated over the three sessions, such that there was a mean decrease in FVC in Session 3. These results indicate that, in subjects with primary Raynaud's disease, there is impairment of the ability of the central nervous system to allow habituation of the cardiovascular components of the alerting response evoked by mild cooling, as with the response to sound. We propose that persistence of the cutaneous vasoconstriction of the alerting response, coupled with increased release of ET-1 secondary to vasoconstriction, prolongs such vasoconstriction and eventually leads to vasospasm.

show abstract

Section: Discussionsupporting

confidence: 92%

Cardiovascular responses evoked by mild cool stimuli in primary Raynaud's disease: the role of endothelin

1999

View full text Add to dashboard Cite

show abstract

“…Thus, our data indicate that the locus of racial differences in vascular reactivity involves vasoconstrictive rather than vasodilatory function. Moreover, inasmuch as cold stress induces peripheral vasoconstriction through an increase in sympathetic stimulation of ␣-adrenergic receptors 12,26 and heat stress induces peripheral vasodilation through a withdrawal of such sympathetic stimulation, 26 our findings imply a racial difference in ␣-adrenergic receptor function rather than a difference in sympathetic efferent discharge. Alternatively, these results may reflect racial differences in nonadrenergic vasoconstrictive mechanisms, involving substances such as angiotensin II or endothelin-1.…”

Section: Discussionmentioning

confidence: 55%

“…Therefore, the present study investigated possible racial differences in cardiac and vascular reactivity during wholebody exposure to a vasoconstrictive cold environment and a vasodilatory hot environment, which elicit opposite changes in sympathetic vasoconstrictor tone. 12,26 …”

mentioning

confidence: 99%

Racial Differences in Hemodynamic Responses to Environmental Thermal Stress Among Adolescents

et al. 2000

View full text Add to dashboard Cite

Background-Previous studies by our laboratory and others have shown that blood pressure (BP) responses to many short-term laboratory stressors are greater in black than in white children. We sought to determine the cardiac and vascular contributions to these differences in BP reactivity and whether racial differences in vascular reactivity involve excessive vasoconstriction or deficient vasodilation. Methods and Results-We evaluated BP, heart rate, and impedance cardiographic measures of preejection period (PEP) and total peripheral resistance (TPR) in healthy black (nϭ76) and white (nϭ60) adolescents (mean age, 14.8 years) during passive exposure to a vasoconstrictive cold chamber (8°C to 10°C) and a vasodilatory heat chamber (40°C to 42°C). Results indicated greater decreases in PEP and increases in TPR in blacks than whites during cold exposure (PϽ0.05) but no group differences during heat exposure. Covariance analyses indicated that the racial differences during cold exposure probably reflected greater ␤-adrenergic cardiac reactivity and ␣-adrenergic vasoconstrictive reactivity in blacks than whites. Conclusions-Blacks and whites exhibited comparable myocardial and vasodilatory responses to heat stress, but blacks exhibited heightened myocardial and vasoconstrictive reactivity to cold stress. These results suggest that the locus of racial differences in vascular reactivity involves vasoconstrictive rather than vasodilatory function. The pattern of racial differences during cold stress raises the possibility that both myocardial and vasoconstrictive mechanisms may contribute to the increased risk of hypertension in blacks.

show abstract

“…In the study of Halperin et al [9] the majority of the subjects with primary Raynaud's disease were women while 50 % of the controls were men. In studies in which the controls and subjects with primary Raynaud's disease were well-matched, finger blood flow was not different in the two groups [20].…”

Section: Figure 5 Effects Of Warming On Cardiovascular Responses Evokmentioning

confidence: 83%

Lack of habituation of the pattern of cardiovascular response evoked by sound in subjects with primary Raynaud’s disease

1998

View full text Add to dashboard Cite

1. The vasospasm of primary Raynaud's disease can be triggered by acute emotional stress. We have studied the pattern of cardiovascular response evoked by acute emotional stress, a sound stimulus of 90 dB, 2 kHz for 30 s, in eight subjects with primary Raynaud's disease and in eight age- and sex-matched controls, the sound being repeated five times on each of days 1, 3 and 5. 2. In controls, the first sound evoked the pattern of the alerting response that is characteristic of acute emotional stress: a rise in arterial pressure and heart rate, a decrease in vascular conductance in the cutaneous circulation of the digit, assessed by laser Doppler recording of erythrocyte (red cell) flux in the digit divided by arterial pressure, and an increase in forearm muscle vascular conductance, assessed from forearm blood flow recorded by venous occlusion plethysmography divided by arterial pressure. 3. In the subjects with primary Raynaud's disease, baselines of arterial pressure, digital cutaneous vascular conductance and forearm vascular conductance were not significantly different from those of the controls and they too showed the alerting response to the first sound, the magnitudes of the changes being comparable to those of the controls. 4. In both the controls and subjects with primary Raynaud's disease, the evoked responses were consistent on repetition of the sound on day 1. In contrast, judging from the means of the changes evoked on each day, the controls showed habituation of the individual components of the alerting response over days 1, 3 and 5, whereas the subjects with primary Raynaud's disease showed no habituation of either the forearm muscle vasodilatation or the digital vasoconstriction. Conversely, the decrease in digital cutaneous vascular conductance evoked by a single deep breath was fully reproducible in both controls and subjects with primary Raynaud's disease when tested at the beginning and end of each experimental day. 5. These results allow the novel conclusion that subjects with primary Raynaud's disease have an abnormality of the central neural modulation of the brain stem areas that integrate the cardiovascular components of the alerting response to acute emotional stress, such that habituation of the vasodilator and vasoconstrictor components of the response on repetition of the stimulus is impaired. We propose that such persistence of vasoconstrictor responses to stressful stimuli predisposes to vasospasm, particularly if neurally mediated vasoconstriction is reinforced by locally released vasoconstrictor factors.

show abstract

Increased α‐Adrenergic responsiveness in idiopathic raynaud's disease

Cited by 69 publications

References 22 publications

Cardiovascular responses evoked by mild cool stimuli in primary Raynaud's disease: the role of endothelin

Cardiovascular responses evoked by mild cool stimuli in primary Raynaud's disease: the role of endothelin

Racial Differences in Hemodynamic Responses to Environmental Thermal Stress Among Adolescents

Lack of habituation of the pattern of cardiovascular response evoked by sound in subjects with primary Raynaud’s disease

Contact Info

Product

Resources

About