| First Author | Sugino H | Year | 2001 |
| Journal | Hypertension | Volume | 37 |
| Issue | 6 | Pages | 1394-8 |
| PubMed ID | 11408383 | Mgi Jnum | J:135009 |
| Mgi Id | MGI:3790250 | Doi | 10.1161/01.hyp.37.6.1394 |
| Citation | Sugino H, et al. (2001) Apoptosis is not increased in myocardium overexpressing type 2 angiotensin II receptor in transgenic mice. Hypertension 37(6):1394-8 |
| abstractText | 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 alpha-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 approximately 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. |
