Subtype specific regulation of human vascular alpha(1)-adrenergic receptors by vessel bed and age
| Autor: | Dan E. Berkowitz, Kelli L. Cozart, Debra A. Schwinn, Habib E. El-Moalem, Leo Marucci, Bonita L. Funk, Elizabeth B. D’Amico, Charlene D. Richardson, Stella O. Page, John V. Booth, Xiaowen L. Rudner, Bradford D. Winters |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Adult
Male medicine.medical_specialty Aging Adrenergic Gene Expression In Vitro Techniques Iliac Artery Piperazines Pathogenesis Phenylephrine Radioligand Assay Hepatic Artery Renal Artery Celiac Artery Physiology (medical) Internal medicine Receptors Adrenergic alpha-1 medicine Humans Saphenous Vein RNA Messenger Mammary Arteries Receptor Adrenergic alpha-Antagonists Aorta Aged Messenger RNA business.industry Arteries Prazosin Middle Aged Femoral Artery Endocrinology medicine.anatomical_structure Spiperone Vasoconstriction Vascular resistance Catecholamine Dopamine Antagonists Female Cardiology and Cardiovascular Medicine business Splanchnic Adrenergic alpha-Agonists Splenic Artery medicine.drug Artery |
| Zdroj: | Circulation. 100(23) |
| ISSN: | 0009-7322 |
| Popis: | Background —α 1 -adrenergic receptors (α 1 ARs) regulate blood pressure, regional vascular resistance, and venous capacitance; the exact subtype (α 1a , α 1b , α 1 d ) mediating these effects is unknown and varies with species studied. In order to understand mechanisms underlying cardiovascular responses to acute stress and chronic catecholamine exposure (as seen with aging), we tested two hypotheses: (1) human α 1 AR subtype expression differs with vascular bed, and (2) age influences human vascular α 1 AR subtype expression. Methods and Results —Five hundred vessels from 384 patients were examined for α 1 AR subtype distribution at mRNA and protein levels (RNase protection assays, ligand binding, contraction assays). Overall vessel α 1 AR density is 16±2.3fmol/mg total protein. α 1a AR predominates in arteries at mRNA ( P P 1 AR mRNA subtype expression varies with vessel bed (α 1a higher in splanchnic versus central arteries, P 1a and α 1b -mediated mammary artery contraction. Overall α 1 AR expression doubles with age (1b >α 1a expression ( P ≤0.001). Conclusions —Human vascular α 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|