Vascular and renal effects of vasopressin and its antagonists in consciousrats with chronic myocardial infarction; evidence for receptor shift

Acute myocardial infarction evokes activation of, among others, the arginin e-vasopressin system, resulting in vasoconstriction and fluid retention. In the present study, the vasoconstrictor and antidiuretic effects of vasopre ssin were examined in vivo in conscious rats with chronic myocardial infarc tion, in the absence or presence of the V-1a receptor antagonist SR-49059 o r the V-2 receptor antagonist OPC-31260. Tn sham rats, vasopressin dose-dep endently 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 rightwar d shift of the dose pressure response curve in sham rats, indicating V-1a r eceptor mediation. This rightward shift by SR-49059 was significantly more in infarcted rats. The suppressed response to the agonist and enhanced sens itivity to the antagonist suggest a reduction of V-1a receptor number in in farcted rats. In both sham and infarcted rats, the urine production after O PC-31260 (337 +/- 14 and 329 +/- 30 mul/min, respectively) was about twice of that in vehicle-treated rats (188 +/- 25 and 155 +/- 24 mul/min, respect ively). However, the response in infarcted rats reached its peak quicker an d lasted for a shorter period, resulting in a 40% lower area under the curv e. Although only measurable during V2 receptor blockade, the reduction of u rine production by vasopressin was significantly more in infarcted compared to sham rats. The enhanced renal response to the agonist and reduced respo nse to the antagonist suggest an increase in V2 receptor number in infarcte d rats. In conclusion, in chronically infarcted rats, vasopressin causes va soconstriction and fluid retention through the V-1a and V-2 receptors, resp ectively. Altered responses after infarction indicate a shift from V-1a to V-2 receptors. (C) 2001 Elsevier Science B.V. All rights reserved.