Role of angiotensin II and vasopressin in cisplatin-induced emesis.
Cisplatin-containing chemotherapy regimens are known to produce intense nausea and vomiting. Angiotensin II (AII) and vasopressin (AVP) have been shown to have emetic properties. The role of these two peptides on cisplatin-induced vomiting was investigated in beagle dogs. Cisplatin (2 mg/kg, IV over 5 min) produced consistent emesis in all dogs after a mean latency time of 144 +/- 4 min. Serum Angiotensin Converting Enzyme (ACE) and plasma AII levels did not significantly change 3 hr after cisplatin administration (at the time of nausea and emesis) in control animals. AVP levels rose from 0.3 pg/ml to 7.5 pg/ml 3 hrs after cisplatin. Complete inhibition of ACE with enalapril (given at 3 mg/kg p.o., 3 hrs prior to cisplatin) reduced AII levels by 70%, but failed to significantly modify the increase in AVP levels (7.2 +/- 2.2 pg/ml), the latency time to emesis (149 +/- 2 min) and the number of emetic episodes induced by cisplatin. These results suggest that AII does not mediate cisplatin-induced emesis, nor does it mediate the increase in AVP observed at the time of emesis. We propose that AVP may be a good marker for nausea and emesis, and that increases in AVP may be neurally-mediated. The large increase in circulating AVP may represent a desirable water conservation response in anticipation of fluid losses induced by vomiting.
Cubeddu
L X
LX
University of North Carolina School of Medicine, Department of Pharmacology, Chapel Hill 27599.
Lindley
C M
CM
Wetsel
W
W
Carl
P L
PL
Negro-Vilar
A
A
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000097:blood / Q000502:physiology*; D000818:Animals; D001127:Arginine Vasopressin / Q000097:blood / Q000502:physiology*; D002945:Cisplatin / Q000009:adverse effects*; D004285:Dogs; D004656:Enalapril / Q000494:pharmacology; D008297:Male; D014839:Vomiting / Q000139:chemically induced*
D000804:Angiotensin II; D001127:Arginine Vasopressin; D004656:Enalapril; D002945:Cisplatin