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EP1 receptors exacerbate mortality in a mouse model of hypertension
Author(s) -
Swan Christina Elizabeth,
Boyd Kelli L,
Zent Roy,
Breyer Richard M
Publication year - 2011
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/fasebj.25.1_supplement.1088.9
Subject(s) - medicine , receptor , blood pressure , angiotensin ii , endocrinology , renin–angiotensin system , prostaglandin , albuminuria , cardiology
C57BL/6 mice with a disrupted Prostaglandin E 2 receptor EP1 allele (EP1−/−; n = 35) or control mice (EP1+/+; n = 58) were uninephrectomized, and 14 days later 50 mg deoxycorticosterone acetate was administered s.c. concurrent with 1% NaCl in the drinking water. Seven days later, angiotensin II (Ang II) was administered (1.5 ng/min/g s.c. Alzet minipump) resulting in high mortality in EP1+/+ mice (60%) with significantly lower mortality in EP1−/− mice (24%, P = 0.004). 35% of EP1+/+ mice but only 10% of EP1−/− mice died of aortic aneurysm rupture. Necropsy revealed overall 65% of EP1+/+ mice and 40% of EP1−/− mice had formation of aortic aneurysms, suggesting the incidence and severity of aortic aneurysms is reduced in EP1−/− mice. Mean intracarotid pressure was reduced in EP1−/− mice vs EP1+/+ two days post‐Ang II minipump implantation (EP1+/+ 128.8 ± 5.1 mmHg n=4, EP1−/− 102.4 ± 7.8 mmHg n=4, P = 0.03). No differences were observed in albuminuria (P = 0.216) or renal histopathology, where moderate hypertensive damage was observed in each group. Thus, this model induces robust hypertension, modest renal damage and significant mortality, with EP1−/− mice being partially protected. Reduction in mortality appears to be associated with a reduction in blood pressure rather than renal protection. Funding was provided by the NIH grants DK37097, DK46205 and GM15431.