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.
Lankhuizen
I M
IM
Department of Pharmacology, Erasmus University Rotterdam Medical Centre EMCR, P.O. Box 1738, 3000 DR. Rotterdam, The Netherlands
van Veghel
R
R
Saxena
P R
PR
Schoemaker
R G
RG
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002908:Chronic Disease; D003243:Consciousness; D003331:Coronary Vessels / Q000601:surgery; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D008026:Ligation / Q000009:adverse effects; D008297:Male; D009203:Myocardial Infarction / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017483:Receptors, Vasopressin / Q000502:physiology; D014554:Urination / Q000187:drug effects; D014563:Urodynamics / Q000187:drug effects; D014667:Vasopressins / Q000494:pharmacology*
D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D007211:Indoles; D011759:Pyrrolidines; D017483:Receptors, Vasopressin; D014667:Vasopressins; C076251:mozavaptan; C082134:relcovaptan