ENDOCRINOLOGIC ABNORMALITIES IN ANGIOTENSINOGEN-GENE KNOCKOUT MICE - STUDIES OF HORMONAL RESPONSES TO DIETARY SALT LOADING

Objective Physiological roles of the renin-angiotensin system in maint aining blood pressure and sodium-water balance in angiotensinogen gene -knockout mice were evaluated with special reference to endogenous pre ssor substances. Methods Angiotensinogen-gene knockout mice and contro l mice were fed a 0.3 or 4% NaCl diet for 2 weeks. Systolic blood pres sure and urinary excretions of electrolytes, creatinine, aldosterone, adrenaline, noradrenaline, dopamine and vasopressin were measured. Res ults About 60% of our angiotensinogen-gene knockout mice did not survi ve until weaning. These mice presented with hypotension and polyuria. Urinary excretion of aldosterone from such mice was significantly lowe r (not detected) than that from control mice (2.0 +/- 0.3 pg/mg creati nine). In contrast, urinary excretion of vasopressin from angiotensino gen-gene knockout mice (0.7 +/- 0.1 ng/mg creatinine) was greater than that from control mice (0.3 +/- 0.1 ng/mg creatinine), and those of a drenaline and of noradrenaline were similar for knockout and control m ice. After salt loading (a 4% NaCl diet), angiotensinogen-gene knockou t mice exhibited a significant increase in systolic blood pressure (fr om 68.3 +/- 2.9 to 95.9 +/- 5.9 mmHg), significant decreases in urinar y excretions of adrenaline (from 65 +/- 8 to 40 +/- 7 pg/mg creatinine ) and noradrenaline (from 467 +/- 48 to 281 +/- 41 pg/mg creatinine) a nd no change in excretion of vasopressin compared with such mice fed a 0.3% NaCl diet. Conclusion The present results with angiotensinogenge ne knockout mice confirm that the renin-angiotensin system plays funda mental roles in maintaining the blood pressure and sodium-water balanc e. Because the vasopressin and catecholaminergic systems may be altere d by lack of angiotensin in angiotensinogen-gene knockout mice, these systems perhaps are not able to restore blood pressure and sodium-wate r depletion to normal levels in these mice. (C) 1998 Rapid Science Ltd .