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Vascular expression of germinal ACE fails to maintain normal blood pressure in ACE–/– mice
Author(s) -
Kessler Sean P.,
deS. Senanayake Preenie,
Gaughan Christina,
Sen Ganes C.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.06-6678com
Subject(s) - medicine , renin–angiotensin system , endocrinology , blood pressure , homeostasis , angiotensin converting enzyme , angiotensin ii , biology
Maintenance of normal blood pressure is critical for preserving the integrity of the cardiovascular system. Angiotensin 1‐converting enzyme (ACE) regulates normal blood pressure and fluid homeostasis through its action in the renin‐angiotensin‐aldosterone system (RAAS) and the renal tubuloglomerular feedback response. Although the two structurally related isozymic forms of ACE both generate the vasoactive octapeptide angiotensin II (Ang II) with equal efficiency, both are expressed in a nonoverlapping tissue‐restricted fashion. To discriminate the precise physiological role of each ACE in its requisite tissue in vivo , we expressed one ACE isoform exclusively in a single cell type of an Ace null mouse. Previously, we demonstrated that vascular endothelial cell‐specific expression of transgenic somatic ACE (sACE) could restore normal blood pressure of Ace‐null mice. In this current study, we expressed germinal ACE (gACE) in the vascular endothelial cells of the Ace null mouse. These mice exhibited correct renal structure, renal function, and normal growth rates. Although the mice had elevated levels of gACE bound to vascular endothelial cells and high levels of gACE and Ang II in the circulating serum, blood pressure was restored only partially. This study demonstrated that gACE, even when expressed in the vasculature, could not functionally substitute for sACE. Kessler, S. P., Senanayake, P. deS., Gaughan, C., Sen, G. C. Vascular expression of germinal ACE fails to maintain normal blood pressure in ACE‐/‐mice. FASEB J. 21, 156–166 (2007)