Expression of human angiotensinogen-renin in rat - effects on transcription and heart function

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Item Type:	Article
Title:	Expression of human angiotensinogen-renin in rat - effects on transcription and heart function
Creators Name:	Bartel, S., Hoch, B., Vetter, D. and Krause, E.G.
Abstract:	In double transgenic rats (dTGR) harboring the human angiotensinogen (hAOGEN) and human renin (hREN) genes, we studied cardiac transcript levels of hypertrophy-related, Ca2+ regulatory, and {beta}-adrenoceptor-associated proteins. The contractile properties and the cellular signaling of isolated hearts exposed to (-)isoproterenol and/or angiotensin (Ang) I were evaluated. dTGR developed hypertension of 174.1±7.6 versus 109.6±2.0 mm Hg (P<0.05) in Sprague-Dawley rats and heart hypertrophy. In hearts of dTGR, the transcript levels of ANP, {beta}-MHC, and α-MHC were altered (percentage versus Sprague-Dawley rats, 100%) by 304%, 178%, and 78%, respectively. Transcript levels of L-type Ca2+ channel, Ca2+ release channel, SERCA2a, phospholamban, Gi- and Gs-proteins were unchanged. Isolated hearts of dTGR indicated higher baseline contractility versus Sprague-Dawley rats. (-)Isoproterenol-modified contractility occurred in both groups; however, the extent (predrug value, 100%) was less in hearts of dTGR versus Sprague-Dawley rats (+dP/dt, 310±42% versus 534±63%; P<0.05). Interestingly, (-)isoproterenol shortened the relaxation time by ≈25% in both groups. This finding was reflected by a protein kinase A-related phospholamban phosphorylation. Ang I depressed the heart contractility but did not interact with the protein kinase A pathway. In conclusion, we have found that expression of the hAOGEN-hREN complex in dTGR elicited specific effects on transcripts of ANP and myofibrillar proteins. Although the β-adrenergically mediated relaxation was not impaired in the hypertrophied hearts, the extent of {beta}-adrenergic inotropic responsiveness was reduced.
Keywords:	Adrenergic Receptor Agonists, Angiotensin I, Contraction, Hypertrophy, Relaxation, Animals, Rats
Source:	Hypertension
ISSN:	0194-911X
Publisher:	American Heart Association
Volume:	39
Number:	2
Page Range:	219-223
Date:	1 January 2002
Official Publication:	https://doi.org/10.1161/hy0202.103275
PubMed:	View item in PubMed

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