Chronic moderate ethanol (ETOH) consumption prevents the development of the age-dependent increase in blood pressure (BP) in both humans and experimental animals. In the present studies, we proposed that the natriuretic peptide family may be partially responsible for this antihypertensive effect of ETOH. The natriuretic system consists of the atrial natriuretic peptide (ANP), the brain natriuretic peptide (BNP), the C-type natriuretic peptide (CNP) and the natriuretic peptide receptors (NPRs). The major function of the natriuretic system is to decrease BP. Thus, the main objective of the present studies was to investigate the interactions of acute and chronic ETOH administration with various components of the natriuretic system. / Acute studies. The injection of 1 and 2 g of ETOH/kg B.W. in Sprague-Dawley rats and 0.25 and 0.50 g of ETOH/kg B.W. in humans resulted in a rapid transient increase of circulating ANP levels. In the rats, this increase in plasma ANP levels was associated with a rapid decrease of atrial ANP content and with a delayed increase in ventricular ANP levels. / Chronic studies. A 20% v/v solution of alcohol was given to spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats for 8 months. In both SHR and WKY rats, chronic ETOH treatment decreased the BP. This lower BP in ETOH-treated animals was associated with lower circulating ANP and BNP levels, whereas ETOH treatment increased atrial ANP and BNP tissue contents, but not ANP and BNP mRNA. Furthermore, chronic ETOH treatment reduced heart ventricular ANP content and ANP mRNA while it increased ventricular BNP content and BNP mRNA in SHR, but not in WKY rats. Chronic ETOH reduced total natriuretic peptide binding sites (NPR-A and NPR-C) in the renal glomeruli. Quantification of the receptor subtypes demonstrated that this decrease was due to the down-regulation of NPR-C. In the renal papilla, chronic ETOH treatment increased natriuretic peptide binding sites (NPR-A). In addition to its effects on the peripheral natriuretic system, chronic ETOH treatment altered the activity of the natriuretic system at the level of the brain. Thus, chronic ETOH increased ANP and CNP levels in the hypothalamus, pons and medulla of SHR rats. In WKY rats, ETOH had no effect on brain ANP levels, but enhanced the concentration of CNP in the hypothalamus and medulla. Chronic ETOH treatment also decreased the affinity of NPR-C in some of the circumventricular organs of the brain, in the subfornical organ and choroid plexus, but not in the area postrema. / These results demonstrate that both acute and chronic moderate ETOH administration alters the activity of various components of the natriuretic system. Therefore, these ETOH-induced modifications in cardiac, renal and brain natriuretic peptides and receptors may contribute to the antihypertensive effect of chronic moderate ETOH drinking.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.42048 |
| Date | January 1997 |
| Creators | Guillaume, Pascal. |
| Contributors | Giaroulakis, C. (advisor), Gutkowska, J. (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Physiology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001549333, proquestno: NQ29953, Theses scanned by UMI/ProQuest. |
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