Cardiovascular endothelins: Essential regulators of cardiovascular homeostasis

Brünner, Friedrich; Brás-Silva, Carmen; Cerdeira, Ana Sofia; Leite‐Moreira, Adelino F.

doi:10.1016/j.pharmthera.2005.11.001

Cited by 157 publications

(158 citation statements)

References 180 publications

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“…4,9,16 These apparently antithetic functions of ETB receptors were previously noticed in other vascular beds and attributed to two distinct functional subtypes of ETB, termed ETB1 (vasodilator) and ETB2 (vasoconstrictor). 32 However, these two ETB receptor subtypes were not fully identified and characterized yet. Recently, it has been clarified that one of the major function of ETB receptors 'in vivo' resides in the active clearance of unbound ET-1: in human subjects undergoing diagnostic cardiac catheterization, infusion of the selective ETB antagonist BQ-788 constricted the microcirculation and increased coronary sinus ET-1 concentrations.…”

Section: Discussionmentioning

confidence: 99%

Effect of sildenafil administration on penile hypoxia induced by cavernous neurotomy in the rat

et al. 2007

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Hypoxia is a normal, physiological condition in penile tissue, which is interrupted by reoxygenation associated to sleep-related erections. We previously described in the rat that a penile fibrosis and overexpression of the pro-fibrotic endothelin-1 type B receptor (ETB) are associated to prolonged (3 months) hypoxia induced by the bilateral surgical resection of the cavernous nerves (bilateral cavernous neurotomy (BCN)). The aim of the present study was to define the time frame in which BCN induces hypoxia and ETB overexpression in the penile tissue. In addition, we studied the timedependency of the rescuing effect of an acute administration of the phosphodiesterase type 5 inhibitor, sildenafil. We found that BCN induced penile hypo-oxygenation (immunohistochemistry for Hypoxyprobe), penile ETB mRNA overexpression (quantitative real-time reverse transcriptase polymerase chain reaction) and hypersensitivity to the ETB agonist IRL-1620 (in vitro contractility study). Sildenafil treatment was able to counteract all these alterations (penile hypoxygenation, hyper-sensitivity to IRL-1620 and ETB overexpression), with its effect being more evident the earlier it was administered.

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Section: Discussionmentioning

confidence: 99%

Effect of sildenafil administration on penile hypoxia induced by cavernous neurotomy in the rat

et al. 2007

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“…EDN1 is expressed in several tissues, including endothelial cells and cardiomyocytes, whereas the expression of endothelin 2 and endothelin 3 seems to be focused on the gastrointestinal tract and on neuronal cells, respectively. 6,7 Only EDN1 is expressed constitutively on vascular endothelium and thereby affects vasomotor tone. 8 DNA sequence variations in the EDN1 gene locus have been reported to be associated with blood pressure levels and hypertension in some populations.…”

mentioning

confidence: 99%

“…9 -12 Increased shear stress because of enhanced blood flow has been proposed as a major mechanism for the blood pressure-lowering effect of exercise training. [13][14][15] Although high shear stress has been shown to inhibit EDN1 expression in endothelial cells, 6 there are few data available on the interactions among the EDN1 locus DNA sequence variation, exercise training, and cardiorespiratory fitness on blood pressure phenotypes. The purpose of the present study was to investigate these interactions in 2 large cohorts: endurance training-induced changes in blood pressure were targeted in the HEalth, RIsk factors, exercise Training And GEnetics (HERITAGE) Family Study and the risk of hypertension was focused on in the Genetics, Fitness, Obesity and Risk of Hypertension (HYPGENE) Study.…”

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confidence: 99%

Effect of Endothelin 1 Genotype on Blood Pressure Is Dependent on Physical Activity or Fitness Levels

et al. 2007

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Abstract-Contributions of the DNA sequence variation at the endothelin 1 locus to the risk of hypertension and to endurance training-induced changes in blood pressure were investigated in the Aerobics Center Longitudinal Study and the Health, Risk Factors, Exercise Training and Genetics Family Study cohorts. We identified 586 normotensive control subjects and 607 incident hypertensive case subjects from the Aerobics Center Longitudinal Study cohort (all whites) who were normotensive and healthy at their first clinic visit. The case subjects were diagnosed with hypertension during an average follow-up of 9.5 years, whereas the control subjects remained normotensive. The allele and genotype frequencies of 5 endothelin 1 haplotype tagging single nucleotide polymorphisms did not differ significantly between the case and control subjects. However, we observed a significant (Pϭ0.0025) interaction between the endothelin 1 rs5370 (G/T; Lys198Asn) genotype and cardiorespiratory fitness level on the risk of hypertension: among low-fit subjects, the rs5370 minor allele (T; 198Asn) was associated with higher risk of hypertension (odds ratio: 1.95; 95% CI: 1.36 to 2.81; Pϭ0.0003), whereas the risk did not differ among genotypes in high-fit subjects. In the white Health, Risk Factors, Exercise Training and Genetics subjects (Nϭ480), the rs5370 T allele was associated with blunted systolic blood pressure (Pϭ0.0046) and pulse pressure (Pϭ0.0016) responses to a 20-week endurance training program. The Lys198Asn variant of the endothelin 1 locus is associated with blood pressure phenotypes in whites. However, the expression of the genotype effect is modulated by physical activity or cardiorespiratory fitness level. Our study provides an illustrative example of how physical activity and fitness level modifies the associations between a candidate gene and outcome phenotype.

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“…Since NO and prostaglandins are important endothelial mediators and are known to be released by the endothelium upon selective ET B1 receptor stimulation [6], these results suggest that these substances probably play an important role modulating the acute diastolic effects of ET-1 in a complex cross-talk between the endothelium and cardiac muscle.…”

Section: The Effects Of Et-1 On Passive Myocardial Propertiesmentioning

confidence: 85%

“…At first regarded as ''the bad guy of circulatory control'' [61], ET-1 is nowadays considered an important regulator of cardiovascular homeostasis (see [6] for a comprehensive review on this topic).…”

Section: Endothelinmentioning

confidence: 99%