gms | German Medical Science

29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

Deutsche Hochdruckliga e. V. DHL ® - Deutsche Hypertonie Gesellschaft Deutsches Kompetenzzentrum Bluthochdruck

23. bis 25.11.2005, Berlin

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The HPA reactivity is attenuated by AT1-antagonism after chronic antihypertensive treatment

Durch chronische antihypertensive Therapie mit einem AT1-Rezeptorantagonisten ist die Rekativität der HPA (Stress)-Achse vermindert

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  • W. Raasch - Universitätsklinikum Schleswig-Holstein, Campus Lübeck (Lübeck, D)
  • C. Wittmershaus - Universitätsklinikum Schleswig-Holstein, Campus Lübeck (Lübeck, D)
  • A. Dendorfer - Universitätsklinikum Schleswig-Holstein, Campus Lübeck (Lübeck, D)
  • O. Jöhren - Universitätsklinikum Schleswig-Holstein, Campus Lübeck (Lübeck, D)
  • A. Ziegler - Universitätsklinikum Schleswig-Holstein, Campus Lübeck (Lübeck, D)
  • P. Dominiak - Universitätsklinikum Schleswig-Holstein, Campus Lübeck (Lübeck, D)

Hypertonie 2005. 29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Berlin, 23.-25.11.2005. Düsseldorf, Köln: German Medical Science; 2006. Doc05hochP61

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/hoch2005/05hoch061.shtml

Published: August 8, 2006

© 2006 Raasch et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

Text

It was shown, that AT1A-receptors were stress-dependently upregulated in hypothalami and adrenals and that AT1-stimulation increased CRH, corticosterone (CORT) and ACTH. Compared to normotensive rats, SHR are more stress sensitive, which was related to an increased AT1A-expression in pituitary glands. The question arose, whether chronic antihypertensive treatment reduces HPA reactivity.

SHR were treated (5 weeks) with candesartan (2mg/kg), ramipril (1) or mibefradil (12). In addition to baseline levels, CORT and ACTH were monitored after CRH-injections (100µg/kg i.v.) over 4h. mRNA of CRH, POMC, AT1A- AT1B- and AT2-receptors was quantified by real time rt-PCR.

Efficacy of treatment was ascertained by equieffective reduction of MAP. Baseline levels of CORT and ACTH were similar in all groups. The CRH-induced ACTH-release (Cmax=641pg/ml) was reduced by candesatan (26%) and ramipril (15%), but not by mibefradil The CORT release of controls (Cmax=327Dng/ml) was consequently diminished only by candesartan (36%) and ramipril (18%). Compared to controls (2.77x106 copies mRNA/100ng cDNA), hypothalamic CRH mRNA was decreased by candesartan (39%) and ramipril (42%). The gene expression of AT1A-, AT1B- and AT2-receptors was not altered by any drug within the HPA-axis.

We conclude, that attenuation of HPA reactivity in SHR is less dependent on normalization of MAP but rather on a sufficient blockade of AT1-receptors, since mibefradil lowers blood pressure but failed to influence CORT or ACTH. The necessity of stress for an effective attenuation of the HPA axis by AT1-blockade is suggested, because only CRH-stimulated but not baseline levels of stress hormones were reduced. Thus, chronic antihypertensive AT1-blockade mainly lessens HPA axis by reduction of pituitary ACTH release. In addition, the participation of a central mechanism is likely due to CRH mRNA downregulation, but needs further investigations. A shift in AT-receptor expression is not participated.