Androgen deprivation, estrogen treatment and vascular function in male rat aorta

Cignarella, Andrea; Bolego, Chiara; Pinna, Christian; Zanardo, Rossella; Nardi, Francesca; Zancan, Valeria; Puglisi, L.

doi:10.1007/s002109900173

Cited by 14 publications

(11 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have recently reported that neither estrogen treatment nor androgen deprivation elicited beneficial effects in terms of vascular reactivity in the aorta from non-diabetic male rats (Cignarella et al 2000). In view of the antithetical results from the present study, one can clearly understand that diabetes is a critical determinant for the vascular effects of sex hormones in both female and male rats.…”

Section: Discussionmentioning

confidence: 64%

“…We recently reported on the effects of sex steroids on vascular function in male non-diabetic rats (Cignarella et al 2000). In the present study, we sought to determine the effects of estrogen treatment on vascular function in male diabetic rats by evaluating aortic responses to a number of vasoactive mediators as well as the generation of vasoactive eicosanoids in both intact and gonadectomized animals.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The influence of sex hormones on vascular responses in the aorta of streptozotocin-diabetic male rats

Cignarella

Bolego

Pinna

et al. 2000

Naunyn-Schmiedeberg's Archives of Pharmacology

Self Cite

View full text Add to dashboard Cite

Diabetes mellitus reduces gender-related differences in the prevalence of cardiovascular disease by fading the vascular protective effects afforded by estrogen in females. However, the impact of estrogen treatment on and the contribution of androgens to vascular function in vessels from male diabetics are largely unknown. We investigated the effects of androgen deficiency and in vivo estrogen treatment by assessing the responsiveness to a number of vasoactive agents and the formation of eicosanoid mediators in aortic rings from intact and castrated streptozotocin-diabetic rats which had been implanted with 17beta-estradiol (E2) or its vehicle for 5 days. Castration was found to attenuate contractility to noradrenaline, to enhance tone-related release of NO, as shown by curves for N-methyl-L-arginine and superoxide dismutase (SOD), and to increase endothelium-dependent relaxation to carbachol and histamine, compared with intact animals. Smooth muscle sensitivity to exogenous NO and platelet thromboxane A2 production were unchanged but prostacyclin release by aortic tissue dropped by about 40% following castration. Treatment with E2 to intact animals still attenuated contractility to noradrenaline and potentiated relaxation to SOD and histamine but affected no other parameters. In contrast, when E2 was administered to castrated animals, responses to SOD, carbachol and histamine were significantly impaired. Thus, androgen deprivation appears to improve vascular function in male diabetic rats, whereas E2 treatment exerts some beneficial effects in intact, but not in castrated animals. Our findings therefore provide new insights into the role of sex hormones in the development of diabetic vascular complications.

show abstract

Section: Discussionmentioning

confidence: 64%

Section: Introductionmentioning

confidence: 99%

The influence of sex hormones on vascular responses in the aorta of streptozotocin-diabetic male rats

Cignarella

Bolego

Pinna

et al. 2000

Naunyn-Schmiedeberg's Archives of Pharmacology

Self Cite

View full text Add to dashboard Cite

show abstract

“…anesthesia. Four weeks later, the castrated animals received a subcutaneous implant of two silastic capsules containing 25 l of vehicle (peanut oil) or E 2 (5.87 g; 0.86 mM) for 5 days (Bolego et al, 1999;Cignarella et al, 2000). Plasma E 2 concentrations after this treatment approached the normal rat proestrus level (Lapchak, 1991).…”

Section: Methodsmentioning

confidence: 99%

The Acute Estrogenic Dilation of Rat Aorta Is Mediated Solely by Selective Estrogen Receptor-α Agonists and Is Abolished by Estrogen Deprivation

Bolego

Cignarella²,

Sanvito³

et al. 2005

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Estrogen is known to induce rapid vasodilatory response in isolated arteries. Because estrogen is a nonselective receptor agonist, the involvement of estrogen receptor (ER) subtypes in acute estrogenic responses has remained elusive. Acute administration of the selective ER␣ agonist 4,4Ј,4Љ-(4-propyl-[ 1 H]pyrazole-1,3,5-triyl) tris-phenol (PPT) to precontracted aortic rings from intact female rats dose-dependently induced an ER-dependent vascular relaxation fully overlapping to that induced by 17␤-estradiol. By contrast, the selective ER␤ agonist 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN) had no acute effect on vasomotion. This short-term vasorelaxant action of PPT was abolished by the NO synthase inhibitor N -nitro-L-arginine methyl ester and by endothelium removal. In aortic tissues from ovariectomized (OVX) rats, however, neither 17␤-estradiol nor PPT induced acute vascular relaxation. The effect of PPT was restored in preparations from estrogen-replaced OVX rats, whereas DPN remained ineffective even after estrogen replacement. PPT acted through an ER-dependent mechanism, as shown by impaired response in the presence of the anti-estrogen ICI 182,780 (7␣,4,5,5,5-pentafluoropentyl)sulfinyl]nonyl]estra-1,3,5(10)-triene-3,17-diol). Accordingly, isolated rat aortic endothelial cells expressed both ER␣ and ER␤. These data show that selective ER␣ but not ER␤ agonists reproduced the acute vasodilation of estrogen via a receptor-mediated pathway in the aorta from intact as well as 17␤-estradiolreplaced OVX rats. This beneficial effect was undetectable in tissues from OVX rats. Selective pharmacological targeting of ER subtypes may thus represent a novel and promising approach in the treatment of vascular disease.The vascular wall is clearly one of the target organs of estrogens. A number of studies have shown that estrogens modulate vasomotor responses after both acute application and in vivo short-or long-term treatment (for review, see Mendelsohn and Karas, 1999;Cignarella et al., 2001). Although different mechanisms have been reported (Shaw et al., 2001), such effects seem to be mediated by specific estrogen receptors (ERs) that are located on the plasma membrane as well as intracellularly. So far, two ER subtypes have been described: ER␣ and ER␤. Both subtypes are found in vascular smooth muscle (Register and Adams, 1998;Hodges et al., 2000;Maggi et al., 2003) and human endothelial cells (Caulin-Glaser et al., 1996). Although similar, the two ER isoforms are distinct gene products with nonoverlapping functions. They are coexpressed in most tissues but increasing evidence suggests that ER␣ and ER␤ mediate opposite effects in a kind of yin-yang manner (Gustafsson, 2003).The relative contribution of each ER subtype to vascular responses has been difficult to investigate because the physiological ER ligand 17␤-estradiol (E 2 ) has no binding affinity preference for ER␣ and ER␤. Selective ER agonists have now become available, the most widely used being 4,4Ј,4Љ-(4-propyl-[1 H]pyrazole-1,3,5-triyl) tris-phen...

show abstract

“…Orchiectomy in male rats has also been demonstrated to have no effect on KCl-induced stress and Ca 2+ influx [39] or phorbol 12,13-dibutyrate-induced contraction [12] . However, it has been reported that contraction to norepinephrine was enhanced in aortae from male rats castrated for 4 weeks [40] . The discrepancies between the different studies may be due to the different hormone deprivation regimen as well as the contracting agent.…”

Section: Discussionmentioning

confidence: 99%

Circulating Sex Hormones Modulate Vascular Contractions and Acute Response to 17β-Estradiol in Rat Mesenteric Arteries

Keung

Man

2011

Pharmacology

View full text Add to dashboard Cite

Aims: We investigated how modification of levels of the sex hormones 17β-estradiol and testosterone affects vascular contraction and nongenomic vascular effects of 17β-estradiol. Methods: Male and female rats were treated with vehicle, 17β-estradiol (25 µg/kg/day) or testosterone (1 mg/kg/day) for 14 consecutive days after sham gonadectomy or gonadectomy was performed. Isometric tensions were then measured from mesenteric arteries of each group of rats. Results: Contraction to phenylephrine was increased in mesenteric arteries from rats with or without gonadectomy treated with testosterone for 14 days compared to their intact controls. Contraction to phenylephrine was reduced in mesenteric arteries of rats with or without gonadectomy treated with 17β-estradiol for 14 days compared to their intact controls. Incubation of mesenteric arteries with 17β-estradiol (1 nmol/l) for 30 min reduced contraction to phenylephrine in mesenteric arteries of rats that were treated with testosterone for 14 days. This acute incubation of 17β-estradiol had no effect on arteries from rats that were treated with 17β-estradiol for 14 days. The acute effect of 17β-estradiol (1 nmol/l) is preserved in arteries without endothelium. Conclusion: Our results suggest that 14 days’ testosterone treatment enhances while 14 days’ 17β-estradiol treatment suppresses contraction as well as the nongenomic effects of 17β-estradiol in the vascular smooth muscles.

show abstract

Androgen deprivation, estrogen treatment and vascular function in male rat aorta

Cited by 14 publications

References 38 publications

The influence of sex hormones on vascular responses in the aorta of streptozotocin-diabetic male rats

The influence of sex hormones on vascular responses in the aorta of streptozotocin-diabetic male rats

The Acute Estrogenic Dilation of Rat Aorta Is Mediated Solely by Selective Estrogen Receptor-α Agonists and Is Abolished by Estrogen Deprivation

Circulating Sex Hormones Modulate Vascular Contractions and Acute Response to 17β-Estradiol in Rat Mesenteric Arteries

Contact Info

Product

Resources

About