Intracellular cAMP increases during the positive inotropism induced by androgens in isolated left atrium of rat

Velasco, Lucía; Sánchez, Manuel; Rubín, José M.; Hidalgo, Agustı́n; Bordallo, Carmen; Cantabrana, Begoña

doi:10.1016/s0014-2999(02)01300-6

Cited by 16 publications

(20 citation statements)

References 25 publications

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“…In the isolated left atria of rats, 5 ␣ -dihydrotestosterone did not bind to the ␤ -adrenoceptors, yet it increased intracellular cAMP levels [10] . In functional studies, it has been reported that increases in cAMP levels were delayed, in comparison to the kinetics of increased cAMP levels in response to isoproterenol, a ␤ -adrenoceptor agonist, and to the beginning of the cardiotonic response to 5 ␣ -dihydrotestosterone [10] .…”

Section: Introductionmentioning

confidence: 90%

“…Androgens have been shown to elicit a cardiotonic effect through a plasma membrane interaction with a pertussis toxin-sensitive G protein [5,8] . Activation of this G protein leads to an intracellular cAMP increase [10] and an increase in intracellular Ca 2+ levels, resulting from Ca 2+ release from intracellular stores in ventricular myocytes [8] .…”

Section: Introductionmentioning

confidence: 99%

“…In functional studies, it has been reported that increases in cAMP levels were delayed, in comparison to the kinetics of increased cAMP levels in response to isoproterenol, a ␤ -adrenoceptor agonist, and to the beginning of the cardiotonic response to 5 ␣ -dihydrotestosterone [10] . Bordallo Phosphodiesterases (PDEs) play an important role in the modulation of heart function via the regulation of intracellular cAMP.…”

Section: Introductionmentioning

confidence: 99%

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Testosterone Inhibits cAMP-Phosphodiesterases in Heart Extracts from Rats and Increases cAMP Levels in Isolated Left Atria

et al. 2011

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Several mechanisms have been proposed to explain the acute cardiovascular effects elicited by androgens, such as vasodilation and positive inotropism. Phosphodiesterases (PDEs) are important modulators of cardiac contractility. However, an effect on PDEs by androgens in cardiac tissues has not previously been reported. In this study, extracts from rat ventricles and isolated left atria were assayed for cAMP-dependent PDE activity. To study the tissue selectivity, the enzymatic activity was also assayed in extracts from bovine tracheal smooth muscle and Chinese hamster ovary (CHO) cells. Functional assays were also performed with isolated atria. Testosterone, but not 5α- and 5β-dihydrotestosterone, inhibited cAMP-PDE activity in extracts from left ventricles and atria. In atria, the inhibition of cAMP-PDE activity was associated with an increase in intracellular levels of cAMP and a cardiotonic response. This effect was not elicited in tracheal muscle strips or CHO cell extracts, suggesting the possibility of tissue and cAMP-PDE selectivity. The results of these studies suggest a new mechanism of action of testosterone in the rat heart, which might contribute to the reported cardiotonic effect.

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Section: Introductionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Testosterone Inhibits cAMP-Phosphodiesterases in Heart Extracts from Rats and Increases cAMP Levels in Isolated Left Atria

et al. 2011

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“…contributed equally to this work. Pharmacology 2004;70:118-122 119 [7][8][9]. In this respect, molecular alternative binding sites of steroids, including androgens, are assumed to be located at the plasma membrane of several cell types [10].…”

Section: Introductionmentioning

confidence: 99%

“…In this respect, molecular alternative binding sites of steroids, including androgens, are assumed to be located at the plasma membrane of several cell types [10]. However, the delay in cAMP increases with respect to the contraction suggests that cAMP-dependent mechanisms may play a role in the maintenance of the contraction, but other mechanisms have to be involved in the initiation of the response [9]. Endogenous ouabain, a steroid with cardiotonic effects, binds to Na + -K + -ATPase at the plasma membrane [11].…”

Section: Introductionmentioning

confidence: 99%

Interaction of Androgens with Cardiotonic Drugs in Isolated Left Atrium of Rat

Secades

Cortina²,

Velasco³

et al. 2004

Pharmacology

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Pharmacological concentrations of androgens are known to elicit a rapid positive inotropism in isolated left atrium of male rats. Upon short-term exposure to androgens, an increase in intracellular cAMP levels has been observed, though delayed with respect to the time course of contraction, suggesting that other mechanisms may participate in initiating the contraction. Therefore, the interaction of positive inotropism elicited by ouabain, an inhibitor of Na⁺-K⁺-ATPase, and androgens was studied in isolated left atrium of rat. Androgens antagonized ouabain-elicited positive inotropism and increased the basal tone. Vanadate, an inhibitor of the Ca²⁺ pump, produced a similar effect as androgens on ouabain-elicited positive inotropism. Therefore, androgens might interact with the Ca²⁺ pump and this may explain the increase in basal tone. The conjugation of 5α-dihydrotestosterone with bovine serum albumin produced the same effect, suggesting an extracellular interaction of androgens inhibiting the Na⁺-K⁺-ATPase that could increase intracellular Ca²⁺ via the Na⁺-Ca²⁺ exchange.

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Mechanisms of Sex Disparities in Cardiovascular Function and Remodeling

Chaudhari

Cushen

Osikoya

et al. 2018

Comprehensive Physiology

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Epidemiological studies demonstrate disparities between men and women in cardiovascular disease prevalence, clinical symptoms, treatments, and outcomes. Enrollment of women in clinical trials is lower than men, and experimental studies investigating molecular mechanisms and efficacy of certain therapeutics in cardiovascular disease have been primarily conducted in male animals. These practices bias data interpretation and limit the implication of research findings in female clinical populations. This review will focus on the biological origins of sex differences in cardiovascular physiology, health, and disease, with an emphasis on the sex hormones, estrogen and testosterone. First, we will briefly discuss epidemiological evidence of sex disparities in cardiovascular disease prevalence and clinical manifestation. Second, we will describe studies suggesting sexual dimorphism in normal cardiovascular function from fetal life to older age. Third, we will summarize and critically discuss the current literature regarding the molecular mechanisms underlying the effects of estrogens and androgens on cardiac and vascular physiology and the contribution of these hormones to sex differences in cardiovascular disease. Fourth, we will present cardiovascular disease risk factors that are positively associated with the female sex, and thus, contributing to increased cardiovascular risk in women. We conclude that inclusion of both men and women in the investigation of the role of estrogens and androgens in cardiovascular physiology will advance our understanding of the mechanisms underlying sex differences in cardiovascular disease. In addition, investigating the role of sex‐specific factors in the development of cardiovascular disease will reduce sex and gender disparities in the treatment and diagnosis of cardiovascular disease. © 2019 American Physiological Society. Compr Physiol 9:375‐411, 2019.

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Intracellular cAMP increases during the positive inotropism induced by androgens in isolated left atrium of rat

Cited by 16 publications

References 25 publications

Testosterone Inhibits cAMP-Phosphodiesterases in Heart Extracts from Rats and Increases cAMP Levels in Isolated Left Atria

Testosterone Inhibits cAMP-Phosphodiesterases in Heart Extracts from Rats and Increases cAMP Levels in Isolated Left Atria

Interaction of Androgens with Cardiotonic Drugs in Isolated Left Atrium of Rat

Mechanisms of Sex Disparities in Cardiovascular Function and Remodeling

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