Importance of the renin-angiotensin system in the regulation of arterial blood pressure in conscious mice and rats.
OBJECTIVE
The present experiments were designed to determine the mechanism(s) for increased sensitivity to blockade of the renin-angiotensin system in mice in comparison with rats.


METHODS
Mice and rats, with indwelling femoral arterial and venous catheters, were chronically administered angiotensin II or pharmacological inhibitors of the renin-angiotensin system as sodium intake was altered.


RESULTS
Increasing sodium intake led to suppression of circulating renin, angiotensin II, and aldosterone in rats and mice in the absence of alterations in arterial blood pressure. Additional experiments demonstrated that continuous intravenous infusion of angiotensin II (20 ng kg(-1) min(-1)) significantly increased arterial blood pressure by approximately 35 mmHg in conscious rats at all levels of sodium intake (n = 6). In contrast, arterial pressure was unaffected by angiotensin II infusion in conscious mice under conditions of low sodium intake, although arterial pressure was increased by 16 mmHg when mice were administered a high sodium intake while infused with angiotensin II (n = 6). In comparison, blockade of the endogenous renin-angiotensin system led to significantly greater effects on arterial pressure in mice than rats. Continuous infusion of captopril (30 microg kg(-1) min(-1)) or losartan (100 microg kg(-1) min(-1)) resulted in a 55-90% greater fall in blood pressure in conscious mice in comparison with conscious rats.


CONCLUSIONS
The present studies indicate that arterial pressure in mice is more dependent upon the endogenous renin-angiotensin system than it is in rats, but mice are more resistant to the hypertensive effects of exogenous angiotensin II.
Cholewa
B C
BC
Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Meister
C J
CJ
Mattson
D L
DL
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice / Q000502:physiology*; D008810:Mice, Inbred C57BL; D051381:Rats / Q000502:physiology*; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D012982:Sodium, Dietary / Q000494:pharmacology; D013045:Species Specificity; D046509:Tissue Culture Techniques; D014661:Vasoconstriction / Q000187:drug effects
D012982:Sodium, Dietary; D000804:Angiotensin II