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 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.

[Arg8]-vasopressin-induced responses on coronary and mesenteric arteries of rats with myocardial infarction: the effects of V1a- and V2-receptor antagonists.

After myocardial infarction, plasma levels of [Arg8]-vasopressin rise to recover hemodynamics. The vascular responses to [Arg8]-vasopressin were studied in vitro in isolated hearts and mesenteric artery segments of rats with 1-day and 3-week-old infarcts, in absence and presence of the V1a-receptor antagonist SR-49059 and the V2-receptor antagonist OPC-31260. Vascular responses of coronary arteries were similar in sham and infarcted hearts. On average, coronary flow was maximally decreased by 70 +/- 3% from baseline values of 11.1 +/- 0.3 ml/min, with pD2 values of 10.52 +/- 0.05. In mesenteric artery segments of sham and infarcted rats, maximal contractile forces, expressed as percentage of contraction to 125 mM KCl, were similar (232 +/- 23% and 239 +/- 8%, respectively). However, pD2 values from infarcted rats (9.22 +/- 0.07) were significantly lower compared with sham (9.55 +/- 0.07) rats. In coronary as well as mesenteric vessels, the vasoconstrictor responses, being more susceptible to SR-49059 (apparent pA2, between 9.12 and 9.82) than to OPC-31260 (apparent pA2, between 6.21 and 6.92), seemed mediated by the V1a receptor. These data indicate that in mesenteric but not in coronary vessels, an altered responsiveness to vasopressin could be observed. Responses are mediated mainly by the V1a receptor.