Activation of the renin-angiotensin system in alpha-calcitonin gene-related peptide/calcitonin gene knockout mice.
OBJECTIVE
To test the hypotheses that circulating or tissue renin-angiotensin system (RAS) activity is increased in alpha-calcitonin gene-related peptide (alpha CGRP) knockout mice, and that this contributes to the increased blood pressure in these mice.


METHODS
Three- to six-month-old male alpha CGRP/calcitonin knockout mice and wild-type controls were studied. Mean arterial pressure (MAP) and its response to an angiotensin II type 1 (AT1) receptor blocker, losartan (3 mg/kg intravenously), were determined in conscious, unrestrained knockout mice and wild-type mice. Radioimmunoassay and western blot were used, respectively, to determine plasma renin activity (PRA) and AT1 receptor protein content in tissues.


RESULTS
Basal MAP and PRA were significantly greater in the knockout mice than in the wild-type mice. In contrast, AT1 receptor content in the renal medulla was significantly decreased in the knockout mice compared with that in wild-type mice. AT1 receptor content in the renal cortex and mesenteric resistance arteries was not different in the knockout and wild-type mice. Losartan produced a significant decrease in MAP in the knockout mice compared with that in wild-type mice.


CONCLUSIONS
Activity of the circulating RAS, but not tissue AT1 receptor expression, is increased in alpha CGRP/calcitonin knockout mice, which may contribute to the increase in blood pressure in this mouse model. The mechanism(s) responsible for the increased activity of the circulating RAS in the absence of alpha CGRP throughout the developmental stages of these animals remains to be determined.
Li
Jianping
J
Department of Medicine and Pharmacology and Toxicology, Michigan State University, East Lansing, 48824, USA.
Zhao
Huawei
H
Supowit
Scott C
SC
DiPette
Donald J
DJ
Wang
Donna H
DH
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D001835:Body Weight; D002116:Calcitonin / Q000235:genetics*; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics*; D006977:Hypertension, Renal / Q000503:physiopathology*; D007668:Kidney / Q000502:physiology; D008297:Male; D008638:Mesenteric Arteries / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009475:Neurons, Afferent / Q000502:physiology; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology*
D044140:Receptor, Angiotensin, Type 1; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide