Subtype Specific Regulation of Human Vascular α
            <sub>1</sub>
            -Adrenergic Receptors by Vessel Bed and Age

Rudner, Xiaowen L.; Berkowitz, Dan E.; Booth, John V.; Funk, B.; Cozart, Kelli L.; D’Amico, Elizabeth B.; El-Moalem, Habib; Page, Stella O.; Richardson, Charlene D.; Winters, Bradford D.; Marucci, Leo; Schwinn, Debra A.

doi:10.1161/01.cir.100.23.2336

Cited by 278 publications

(228 citation statements)

References 21 publications

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“…For example, Hussain and Marshall found in vitro that the a 1D -AR predominated in several systemic rat vessels, 46 which may not be the case in humans. 47 Tong and Cheng found a 1A -ARs to be responsible for the contractile response of rat corpus cavernosum, which does not seem to be in agreement with the in vivo data. 48 Expression of mRNA for a 2A -, a 2B -, and a 2C -ARs in whole human corpus cavernosum tissue has been demonstrated, a 2A -ARs predominating.…”

Section: Contraction-mediating Transmitters and Receptorsmentioning

confidence: 72%

Neurotransmitters: central and peripheral mechanisms

2000

Int J Impot Res

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Re¯exive erection initiated by recruitment of penile afferents, involves both autonomic and somatic efferents. The re¯ex is mediated at the spinal cord level, modulated by supraspinal in¯uences, and may use several transmitters. Dopamine, acetylcholine, nitric oxide, and peptides, such as oxytocin and ACTHaa-MSH, seem to have a facilitatory role, whereas serotonin may be either facilitatory or inhibitory, and enkephalins are inhibitory. Peripherally, the balance between contractant and relaxant factors controls the degree of contraction of the smooth muscle of the corpora cavernosa, and determines the functional state of the penis. Noradrenaline contracts both corpus cavernosum and penile vessels via stimulation of a 1 -adrenoceptors. The role of endothelins in the control of penile smooth muscle tone is presently unclear. Neurogenic nitric oxide (NO) is considered the most important factor for relaxation of penile vessels and corpus cavernosum. The role of other mediators, released from nerves or endothelium has not been de®nitely established.

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Section: Contraction-mediating Transmitters and Receptorsmentioning

confidence: 72%

Neurotransmitters: central and peripheral mechanisms

2000

Int J Impot Res

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“…Various a1-adrenergic receptor subtypes have been identified in the lower urinary tract, including a1A and a1D receptors in prostatic stromal cells, 26,27 a1B receptors in epithelial cells, a1A and a1B receptors in vascular smooth muscle, 28 a1A and a1D receptors in the urethra and bladder and a1D receptors in the detrusor muscle. 29 Penile erection and flaccidity depend on a balance between contraction and relaxation of the corpus cavernosum smooth muscle.…”

Section: Luts and Ed: Pathophysiological Correlationsmentioning

confidence: 99%

“…31 In certain human arteries, a1-receptor expression increases and the relative proportion of a1-adrenergic receptor subtypes is modulated by aging. 28 These changes might be happening as well in the human prostatic, bladder and erectile tissue. The contractile response of the smooth muscle strips to phenylephrine was greater for those strips isolated from the corpus cavernosum of older (460 years) men with ED than for those isolated from younger (o60 years) men with ED.…”

Section: Luts and Ed: Pathophysiological Correlationsmentioning

confidence: 99%

Association of lower urinary tract symptoms and erectile dysfunction: pathophysiological aspects and implications for clinical management

2011

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There is strong evidence from multiple epidemological studies that lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) are correlated, independent of age or comorbidities as diabetes or hypertension. Although a direct causal relationship is not established yet, four pathophysio logical mechanisms can explain the relationship. These include alteration in nitric oxide bioavailability, a1-adrenergic receptor hyperactivity, pelvic atherosclerosis and sex hormones. This association has different clinical implications on the management of both disorders. Men seeking care for one condition should always be screened for complaints of the other condition. Sexual function should be assessed and discussed with the patient when choosing the appropriate management strategy for LUTS, as well as when evaluating the patient's response to treatment. Multiple large clinical trials have shown an improvement in LUTS after phosphodiesterase-5 (PDE5)-inhibitor treatment. PDE5 inhibitors show promise as a future treatment for LUTS, either in conjunction with existing therapies or as a primary treatment. There may be a potential therapeutic role for testosterone in LUTS treatment in cases of testosterone deficiency that needs to be investigated. Much further investigation is required, but it is evident that the association between LUTS and ED is fundamental for future therapies and possible preventative strategies.

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“…Studies showed that a1A-adrenoceptors mediated the contractions of both animal and human blood vessels. [10][11][12][13] Animal studies also indicated that the a1A-adrenoceptor subtype was required for normal arterial blood pressure regulation. ADRA1A gene knockout (KO) mice exhibited an 8-12% reduction in blood pressure depending on gene copy numbers.…”

Section: Discussionmentioning

confidence: 99%

Arg347Cys polymorphism of α1A-adrenoceptor gene is associated with blood pressure response to nifedipine GITS in Chinese hypertensive patients

et al. 2009

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Our objectives were to evaluate whether polymorphisms in the a1A-and b2-adrenoceptor genes influence blood pressure response to nifedipine gastrointestinal therapeutic system (GITS). Hypertensive patients received daily treatment with an oral dosage of 30 mg nifedipine GITS for 16 days. Genotypes of the Arg347Cys polymorphism in the a1A-adrenoceptor gene and the Arg16Gly and Gln27Glu polymorphisms in the b2-adrenoceptor gene were determined by TaqMan single-nucleotide polymorphism genotyping assay. The sixteenth-day steady-state plasma concentration of nifedipine was measured using HPLC with UV detection. Multivariate linear regression was performed in a total of 447 patients to evaluate the effects of these polymorphisms on blood pressure response to nifedipine GITS. Patients carrying the Cys347 allele of the a1A-adrenoceptor gene had a greater systolic blood pressure reduction than did those carrying two Arg347 alleles of the a1A-adrenoceptor gene (32.5±14.0 versus 27.3±15.5 mm Hg, respectively, P¼0.006). However, diastolic blood pressure reduction was not associated with the Arg347Cys polymorphism in the a1A-adrenoceptor gene. In addition, no significant associations were observed between blood pressure reduction and two polymorphisms in the b2-adrenoceptor gene. Our data suggest that the Arg347Cys polymorphism in the a1A-adrenoceptor gene may be used to predict blood pressure response to nifedipine GITS in

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Subtype Specific Regulation of Human Vascular α ₁ -Adrenergic Receptors by Vessel Bed and Age

Abstract: Human vascular alpha(1)AR subtype distribution differs from animal models, varies with vessel bed, correlates with contraction in mammary artery, and is modulated by aging. These findings provide potential novel targets for therapeutic intervention in many clinical settings.

Cited by 278 publications

References 21 publications

Neurotransmitters: central and peripheral mechanisms

Neurotransmitters: central and peripheral mechanisms

Association of lower urinary tract symptoms and erectile dysfunction: pathophysiological aspects and implications for clinical management

Arg347Cys polymorphism of α1A-adrenoceptor gene is associated with blood pressure response to nifedipine GITS in Chinese hypertensive patients

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Subtype Specific Regulation of Human Vascular α 1 -Adrenergic Receptors by Vessel Bed and Age

Abstract: Human vascular alpha(1)AR subtype distribution differs from animal models, varies with vessel bed, correlates with contraction in mammary artery, and is modulated by aging. These findings provide potential novel targets for therapeutic intervention in many clinical settings.

Cited by 278 publications

References 21 publications

Neurotransmitters: central and peripheral mechanisms

Neurotransmitters: central and peripheral mechanisms

Association of lower urinary tract symptoms and erectile dysfunction: pathophysiological aspects and implications for clinical management

Arg347Cys polymorphism of α1A-adrenoceptor gene is associated with blood pressure response to nifedipine GITS in Chinese hypertensive patients

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Product

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Subtype Specific Regulation of Human Vascular α ₁ -Adrenergic Receptors by Vessel Bed and Age