In:
Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 37, No. 6 ( 2001-06), p. 1394-1398
Abstract:
Abstract —To determine whether angiotensin type 2 (AT 2 ) receptor stimulation induces apoptosis in cardiomyocytes in vivo, we developed transgenic mice overexpressing the AT 2 receptor in a cardiac-specific manner, using the α-myosin heavy-chain promoter. Ten- to 12-week-old male homozygous transgenic mice (n=44) and wild-type mice (n=44) were used. Both transgenic and wild-type mice were given either saline (control), a subpressor dose of angiotensin II (100 ng · kg −1 · min −1 ), a pressor dose of angiotensin II (1000 ng · kg −1 · min −1 ) for 14 days, a pressor dose of angiotensin II for 28 days to investigate the effects of stimulation on both angiotensin type 1 (AT 1 ) and AT 2 receptors, the AT 1 antagonist L158809 alone, or a combination of angiotensin II (1000 ng · kg −1 · min −1 ) and L158809 for 14 days to investigate the effects of selective AT 2 receptor stimulation. Apoptosis was analyzed in paraffin-embedded ventricular sections by the terminal deoxynucleotidyl-transferase–mediated dUTP nick-end labeling (TUNEL) technique. In both transgenic and wild-type mice, administration of a subpressor dose of angiotensin II, L158809 , or a combination of angiotensin II and L158809 did not significantly affect the tail-cuff blood pressure or heart-to-body weight ratio, whereas administration of a pressor dose of angiotensin II for 14 or 28 days significantly increased blood pressure and the heart-to-body weight ratio. However, there was no statistical difference between the effects of angiotensin II in transgenic and wild-type mice. The number of TUNEL-positive nuclei was ≈0 to 10 per 100 000 cardiomyocytes, with no difference between transgenic and wild-type mice, regardless of saline infusion or any stimulation. In infarcted canine myocardial tissue sections for positive control, the number of TUNEL-positive nuclei was increased by 13.8 to 19.1 times compared with those in the noninfarcted myocardium. In conclusion, angiotensin II infusion for a period of 28 days failed to induce cardiomyocyte apoptosis regardless of the presence or absence of cardiac AT 2 receptor overexpression. It is unlikely that in mice the AT 2 receptor is a strong signal to induce cardiomyocyte apoptosis in vivo.
Type of Medium:
Online Resource
ISSN:
0194-911X
,
1524-4563
DOI:
10.1161/01.HYP.37.6.1394
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2001
detail.hit.zdb_id:
2094210-2
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