title: Effects of alpha1-adrenergic receptor blockade by doxazosin on renin-angiotensin system-regulating aminopeptidase and vasopressin-degrading activities in male and female rat thalamus.
abstract: The thalamus has connections with central autonomic centers involved in cardiovascular control and is enervated by noradrenergic fibers. The excitability of thalamic neurons is due to a reduction of ionic currents mediated by alpha(1)-adrenoceptors. The brain renin- angiotensin system (RAS) and the peptide hormone arginine-vasopressin (AVP) are also involved in the central control of blood pressure, and fluid and electrolyte homeostasis. It has been extensively reported that aminopeptidase A (APA), aminopeptidase B (APB), aminopeptidase N (APN), and vasopressin-degrading cystyl aminopeptidase activity (AVP-DA) play an important role in the regulation of the activity of angiotensins and AVP. We have analyzed the effect of alpha(1)-adrenoceptor blockade by doxazosin on RAS-regulating aminopeptidase activities and AVP-DA in soluble and membrane-bound fractions of male and female rat thalamus. Our results show that alpha(1)-adrenoceptors blockade by doxazosin does not modify the RAS through its degrading peptidases at thalamic level either in male or female rats. However, alpha(1)-adrenoceptors blockade shows gender differences in AVP-DA, increasing in males but not in females, supporting an increased capacity of males against females to degrade AVP and, therefore, to regulate cardiovascular homeostasis, under this pharmacological manipulation.
authors.affiliation: Experimental and Clinical Physiopathology Research Group, Department of Health Sciences, Faculty of Experimental and Health Sciences, University of Jaén, Jaén, Spain.
authors.forename: S
authors.initials: S
authors.lastname: de la Chica-Rodríguez
authors.forename: P
authors.initials: P
authors.lastname: Cortés-Denia
authors.forename: M J
authors.initials: MJ
authors.lastname: Ramírez-Expósito
authors.forename: J M
authors.initials: JM
authors.lastname: Martínez-Martos
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000626:Aminopeptidases / Q000187:drug effects / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism*; D018826:CD13 Antigens / Q000187:drug effects / Q000378:metabolism; D002320:Cardiovascular Physiological Phenomena; D010122:Cystinyl Aminopeptidase / Q000187:drug effects / Q000378:metabolism; D017292:Doxazosin / Q000494:pharmacology*; D005260:Female; D043384:Glutamyl Aminopeptidase / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000187:drug effects; D012737:Sex Factors; D018709:Statistics, Nonparametric; D013788:Thalamus / Q000187:drug effects / Q000201:enzymology*
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D018340:Receptors, Adrenergic, alpha-1; D001127:Arginine Vasopressin; D000626:Aminopeptidases; D018826:CD13 Antigens; D010122:Cystinyl Aminopeptidase; C019721:aminopeptidase B; D043384:Glutamyl Aminopeptidase; D017292:Doxazosin