Chronic ACE inhibition by quinapril modulates central vasopressinergic system

Frank Muders, Dietmar Elsner, Karin Jandeleit, Udo Bahner, Eckhard P. Kromer, Ingrid Kirst, Günter A.J. Riegger, Miklos Palkovits

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Objective: The role of the brain as a target for angiotensin converting enzyme (ACE) inhibitors in the treatment of heart failure and hypertension is unclear. To test the hypothesis that ACE inhibitors may modulate other central neuropeptide systems such as the central vasopressin system, we studied the effects of chronic treatment with the ACE inhibitor, quinapril, on ACE activity and on central vasopressin content in specific brain areas in rats. Methods: 22 rats were chronically treated with quinapril (6 mg · kg- 1 BW per garage daily for 6 weeks; untreated controls, n = 14). ACE density in various brain regions was assessed by in vitro autoradiography using the specific ACE inhibitor, 125I-351A. Vasopressin content was determined in 19 brain areas (micropunch technique) known to be involved in cardiovascular regulation. Results: Following chronic quinapril treatment ACE was significantly decreased in the thalamus (- 38%), hypothalamus (- 37%), hypophysis (- 35%), cerebellum (- 36%), choroid plexus (- 20%), and locus coeruleus (- 35%). Additionally, a marked reduction in serum ACE activity (- 97%) was observed. Plasma levels of vasopressin were significantly decreased after quinapril treatment (0.97[s.e.m. 0.11] vs. 1.63[0.24] pg · ml-1 in controls, P < 0.05). Vasopressin content was significantly reduced in 9 of 19 specific brain areas. Regarding the hypothalamic vasopressin-producing nuclei, vasopressin was decreased in the paraventricular (292[197] vs. 2379[585] pg · mg-1 protein in controls; P <0.001) and supraoptic nuclei (13618[1979] vs. 24525[3894] pg · mg-1 protein; P < 0.05), but not in the suprachiasmatic nucleus. Vasopressin content was significantly reduced in brain areas connected by vasopressinergic fibres originating in the hypothalamic paraventricular nucleus: namely central gray, subcommissural organ, organum vasculosum laminae terminalis, dorsal raphe nucleus, and locus coeruleus. Vasopressin content was also significantly reduced in the median eminence (5887[1834] vs. 28321[4969] pg · mg-1 protein, P < 0.001), where the hormone is mainly concentrated in the hypothalamo-hypophysial tract. Conclusions: Autoradiographic studies in vitro indicate that orally administered quinapril suppresses central ACE activity after chronic treatment. ACE inhibition by quinapril strongly influences vasopressin content in important brain areas which are involved in central cardiovascular regulation. Therefore, central modulatory effects of ACE inhibitors may also contribute to overall therapeutic efficacy.

Original languageEnglish
Pages (from-to)575-581
Number of pages7
JournalCardiovascular research
Volume34
Issue number3
DOIs
Publication statusPublished - Jun 1 1997

Keywords

  • ACE
  • ACE inhibitors
  • Brain nuclei
  • Central cardiovascular regulation
  • Rat
  • Vasopressin

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Chronic ACE inhibition by quinapril modulates central vasopressinergic system'. Together they form a unique fingerprint.

  • Cite this

    Muders, F., Elsner, D., Jandeleit, K., Bahner, U., Kromer, E. P., Kirst, I., A.J. Riegger, G., & Palkovits, M. (1997). Chronic ACE inhibition by quinapril modulates central vasopressinergic system. Cardiovascular research, 34(3), 575-581. https://doi.org/10.1016/S0008-6363(97)00084-9