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

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 V1a receptor antagonist SR-49059 or the V2 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 V1a 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 V1a receptor number in infarcted rats. In both sham and infarcted rats, the urine production after OPC-31260 (337±14 and 329±30 μl/min, respectively) was about twice of that in vehicle-treated rats (188±25 and 155±24 μl/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 V2 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 V2 receptor number in infarcted rats. In conclusion, in chronically infarcted rats, vasopressin causes vasoconstriction and fluid retention through the V1a and V2 receptors, respectively. Altered responses after infarction indicate a shift from V1a to V2 receptors.

• View at Publisher
• View at Pubmed
• View at Scopus
• View at Web of Science