Treatment with cilazapril, angiotensin-converting enzyme inhibitor, changes the affinity of arginine vasopressin receptor in the kidney of the spontaneously hypertensive rat.
To elucidate the interaction between the renin-angiotensin system and arginine vasopressin (AVP), we investigated the change in the renal AVP receptor in the spontaneously hypertensive rat (SHR) treated with an angiotensin-converting enzyme (ACE) inhibitor, cilazapril. SHR (age 15 weeks) were given oral cilazapril 10 mg/kg body weight daily for 25 days (ACEI group). Systolic blood pressure was significantly decreased in the ACEI group as compared with the untreated SHRs (control group) after day 2. Urine volume in the ACEI group was 3- to 5-fold higher than that in the control group. Under these conditions, the renal AVP receptor was studied using the radiolabeled receptor assay (RRA) of [3H]-AVP from renal medulla membrane fractions. The serum concentrations of sodium, potassium, chloride, urea nitrogen and creatinine were not significantly different between the two groups. The plasma concentration of AVP in the ACEI group was higher than that in the control group. The dissociation constant (Kd) in the ACEI group was significantly lower than that in the control, although there was no significant change of maximum binding capacity (Bmax) between the two groups. We previously reported that the number of renal AVP receptors decreased in rats with diabetes insipidus which were treated with lithium, suggesting that the change in the AVP receptor is a primary cause of polyuric state induced by lithium. In the present study, the diuretic state and the decrease in blood pressure induced by cilazapril resulted in a marked decrease in the Kd of the renal AVP receptor and an increase in the plasma AVP level. It is suggested that plasma AVP and renal AVP receptors in SHR responded to the diuretic state induced by cilazapril by increasing the secretion and renal receptor affinity. We conclude that the AVP system plays an important role in the regulation of the fluid balance under diuretic conditions caused by ACE inhibitor treatment.
Nishida
N
N
Third Department of Internal Medicine, Okayama University Medical School, Japan.
Ogura
T
T
Yamauchi
T
T
Hosoya
M
M
Ota
Z
Z
D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D017315:Cilazapril / Q000494:pharmacology / Q000627:therapeutic use*; D004231:Diuresis / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D017483:Receptors, Vasopressin / Q000187:drug effects / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000502:physiology
D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D017315:Cilazapril