Although the vasodilatory response during mental stress is blunted in heart failure (HF), the mechanisms underlying this phenomenon are not fully understood. We tested the hypothesis that sympathetic ...activity limits the endothelium-dependent vasodilatation during mental stress in chronic HF patients. Twenty-one HF patients (age 45 +/- 2 yr, functional classes III and IV, New York Heart Asssociation) and 22 age-matched normal controls (NC; age 42 +/- 2 yr, P = 0.13) were studied at rest and during 4 min of Stroop color-word test with brachial intra-arterial saline, acetylcholine (endothelium dependent), phentolamine ({alpha}-blocker), and phentolamine plus acetylcholine infusion. Forearm blood flow was measured by venous occlusion plethysmography. Baseline forearm vascular conductance (FVC) was significantly lower in HF patients (2.18 +/- 0.12 vs. 3.66 +/- 0.22 units, P = 0.001). During mental stress with saline, the changes in FVC were significantly blunted in HF patients compared with NC (0.92 +/- 0.20 vs. 2.13 +/- 0.39 units, P = 0.001). In HF, the vasodilatation with acetylcholine was similar to saline control and significantly lower than in NC. In HF patients, phentolamine significantly increased FVC responses (1.16 +/- 0.20 vs. 2.09 +/- 0.29 units, P = 0.001), and the difference between HF patients and NC tended to decrease (2.09 +/- 0.29 vs. 3.61 +/- 0.74 units, P = 0.052). The vasodilatation with phentolamine plus acetylcholine was similar between HF and NC (4.23 +/- 0.73 vs. 4.76 +/- 1.03 units, P = 0.84). In conclusion, sympathetic activation mediates the blunted muscle endothelium-mediated vasodilatation during mental stress in HF patients. PUBLICATION ABSTRACT
We hypothesized that the muscle vasodilatation during mental stress and exercise would vary among humans who are polymorphic at alleles 16 and 27 of the beta(2)-adrenoceptors. From 216 preselected ...volunteers, we studied 64 healthy, middle-aged normotensive women selected to represent three genotypes: homozygous for the alleles Arg(16) and Gln(27) (Arg(16)/Gln(27), n = 34), Gly(16) and Gln(27) (Gly(16)/Gln(27), n = 20), and Gly(16) and Glu(27) (Gly(16)/Glu(27), n = 10). Forearm blood flow (plethysmography) and muscle sympathetic nerve activity (microneurography) were recorded during 3-min Stroop color-word test and 3-min handgrip isometric exercise (30% maximal voluntary contraction). Baseline muscle sympathetic nerve activity, forearm vascular conductance, mean blood pressure, and heart rate were not different among groups. During mental stress, the peak forearm vascular conductance responses were greater in Gly(16)/Glu(27) group than in Gly(16)/Gln(27) and Arg(16)/Gln(27) groups (1.79 +/- 0.66 vs. 0.70 +/- 0.11 and 0.58 +/- 0.12 units, P = 0.03). Similar results were found during exercise (0.80 +/- 0.25 vs. 0.28 +/- 0.08 and 0.31 +/- 0.08 units, P = 0.02). Further analysis in a subset of subjects showed that brachial intra-arterial propranolol infusion abolished the difference in vasodilatory response between Gly(16)/Glu(27) (n = 6) and Arg(16)/Gln(27) (n = 7) groups during mental stress (0.33 +/- 0.20 vs. 0.46 +/- 0.21 units, P = 0.50) and exercise (0.08 +/- 0.06 vs. 0.03 +/- 0.03 units, P = 0.21). Plasma epinephrine concentration in Arg(16)/Gln(27) and Gly(16)/Glu(27) groups was similar. In conclusion, women who are homozygous for Gly(16)/Glu(27) of the beta(2)-adrenoceptors have augmented muscle vasodilatory responsiveness to mental stress and exercise.
1 Heart Institute (InCor), Medical School, 2 Department of Endocrinology, and 3 School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil
Submitted 17 May 2004
; accepted in ...final form 15 October 2004
We hypothesized that the muscle vasodilatation during mental stress and exercise would vary among humans who are polymorphic at alleles 16 and 27 of the 2 -adrenoceptors. From 216 preselected volunteers, we studied 64 healthy, middle-aged normotensive women selected to represent three genotypes: homozygous for the alleles Arg 16 and Gln 27 (Arg 16 /Gln 27 , n = 34), Gly 16 and Gln 27 (Gly 16 /Gln 27 , n = 20), and Gly 16 and Glu 27 (Gly 16 /Glu 27 , n = 10). Forearm blood flow (plethysmography) and muscle sympathetic nerve activity (microneurography) were recorded during 3-min Stroop color-word test and 3-min handgrip isometric exercise (30% maximal voluntary contraction). Baseline muscle sympathetic nerve activity, forearm vascular conductance, mean blood pressure, and heart rate were not different among groups. During mental stress, the peak forearm vascular conductance responses were greater in Gly 16 /Glu 27 group than in Gly 16 /Gln 27 and Arg 16 /Gln 27 groups (1.79 ± 0.66 vs. 0.70 ± 0.11 and 0.58 ± 0.12 units, P = 0.03). Similar results were found during exercise (0.80 ± 0.25 vs. 0.28 ± 0.08 and 0.31 ± 0.08 units, P = 0.02). Further analysis in a subset of subjects showed that brachial intra-arterial propranolol infusion abolished the difference in vasodilatory response between Gly 16 /Glu 27 ( n = 6) and Arg 16 /Gln 27 ( n = 7) groups during mental stress (0.33 ± 0.20 vs. 0.46 ± 0.21 units, P = 0.50) and exercise (0.08 ± 0.06 vs. 0.03 ± 0.03 units, P = 0.21). Plasma epinephrine concentration in Arg 16 /Gln 27 and Gly 16 /Glu 27 groups was similar. In conclusion, women who are homozygous for Gly 16 /Glu 27 of the 2 -adrenoceptors have augmented muscle vasodilatory responsiveness to mental stress and exercise.
exercise;; muscle vasodilatation
Address for reprint requests and other correspondence: C. E. Negrão, Instituto do Coração (InCor), Unidade de Reabilitação Cardiovascular e Fisiologia do Exercício, Av. Dr. Enéas de Carvalho Aguiar, 44, Cerqueira César, São Paulo, SP, CEP 05403000, Brazil (E-mail: cndnegrao{at}incor.usp.br )
We hypothesized that the muscle vasodilatation during mental stress and exercise would vary among humans who are polymorphic at alleles 16 and 27 of the β
2
-adrenoceptors. From 216 preselected ...volunteers, we studied 64 healthy, middle-aged normotensive women selected to represent three genotypes: homozygous for the alleles Arg
16
and Gln
27
(Arg
16
/Gln
27
, n = 34), Gly
16
and Gln
27
(Gly
16
/Gln
27
, n = 20), and Gly
16
and Glu
27
(Gly
16
/Glu
27
, n = 10). Forearm blood flow (plethysmography) and muscle sympathetic nerve activity (microneurography) were recorded during 3-min Stroop color-word test and 3-min handgrip isometric exercise (30% maximal voluntary contraction). Baseline muscle sympathetic nerve activity, forearm vascular conductance, mean blood pressure, and heart rate were not different among groups. During mental stress, the peak forearm vascular conductance responses were greater in Gly
16
/Glu
27
group than in Gly
16
/Gln
27
and Arg
16
/Gln
27
groups (1.79 ± 0.66 vs. 0.70 ± 0.11 and 0.58 ± 0.12 units, P = 0.03). Similar results were found during exercise (0.80 ± 0.25 vs. 0.28 ± 0.08 and 0.31 ± 0.08 units, P = 0.02). Further analysis in a subset of subjects showed that brachial intra-arterial propranolol infusion abolished the difference in vasodilatory response between Gly
16
/Glu
27
( n = 6) and Arg
16
/Gln
27
( n = 7) groups during mental stress (0.33 ± 0.20 vs. 0.46 ± 0.21 units, P = 0.50) and exercise (0.08 ± 0.06 vs. 0.03 ± 0.03 units, P = 0.21). Plasma epinephrine concentration in Arg
16
/Gln
27
and Gly
16
/Glu
27
groups was similar. In conclusion, women who are homozygous for Gly
16
/Glu
27
of the β
2
-adrenoceptors have augmented muscle vasodilatory responsiveness to mental stress and exercise.
