Acute
myocardial infarction evokes activation of, among others, the
arginine-vasopressin system, resulting in vasoconstriction and fluid retention. In the present study, the
vasoconstrictor and
antidiuretic effects of
vasopressin were examined in vivo in conscious rats with chronic
myocardial infarction, in the absence or presence of the V(1a) receptor antagonist
SR-49059 or the V(2) receptor antagonist
OPC-31260. In
sham rats,
vasopressin dose-dependently increased mean arterial pressure (maximum response: 45+/-3 mm Hg), which was significantly suppressed in infarcted rats (maximum response: 32+/-3 mm Hg).
SR-49059, but not
OPC-31260, caused a significant rightward shift of the dose pressure response curve in
sham rats, indicating V(1a) receptor mediation. This rightward shift by
SR-49059 was significantly more in infarcted rats. The suppressed response to the agonist and enhanced sensitivity to the antagonist suggest a reduction of V(1a) receptor number in infarcted rats. In both
sham and infarcted rats, the urine production after
OPC-31260 (337+/-14 and 329+/-30 microl/min, respectively) was about twice of that in vehicle-treated rats (188+/-25 and 155+/-24 microl/min, respectively). However, the response in infarcted rats reached its peak quicker and lasted for a shorter period, resulting in a 40% lower area under the curve. Although only measurable during V(2) receptor blockade, the reduction of urine production by
vasopressin was significantly more in infarcted compared to
sham rats. The enhanced renal response to the agonist and reduced response to the antagonist suggest an increase in V(2) receptor number in infarcted rats. In conclusion, in chronically infarcted rats,
vasopressin causes vasoconstriction and fluid retention through the V(1a) and V(2) receptors, respectively. Altered responses after
infarction indicate a shift from V(1a) to V(2) receptors.