Changes in reactivity towards 5-hydroxytryptamine in the renal vasculature of the diabetic spontaneously hypertensive rat.
BACKGROUND
Diabetes and hypertension are both associated with an increased risk of renal disease. The combination of these diseases produces marked acceleration of the problems.


OBJECTIVE
To examine the reactivity in the renal vasculature of diabetic hypertensive rats.


METHODS
We investigated the reactivity towards 5-hydroxytryptamine (5-HT) in Krebs solution-perfused kidneys of diabetic normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). In addition, the interaction between the thromboxane A2 mimetic U46619 and 5-HT was examined.


RESULTS
Discrete dose-response curves were obtained for the response to 5-HT (0.1-30 micrograms/g kidney) in Krebs solution-perfused kidneys of control and diabetic WKY rats and SHR. The following order of reactivity was determined: control SHR > diabetic SHR > control WKY rats = diabetic WKY rats. The thromboxane A2 mimetic U46619 (10 ng/ml) potentiated responses to 5-HT significantly in kidneys of diabetic WKY rats and control SHR, but not in kidneys from control WKY rats and diabetic SHR.


CONCLUSIONS
The differential affected reactivity towards 5-HT kidneys from diabetic and hypertensive rats might be due to previously documented differences in receptor number. The marked effect of U46619 on the reactivity towards 5-HT in kidneys of diabetic and control rats indicates that this interaction might be important given the increased levels of thromboxane A2 reported to occur in these diseases. The reason for the lack of effect of thromboxane/prostaglandin receptor stimulation on responses to 5-HT in the combined model (i.e. diabetic hypertensive rats) needs to be determined.
Boston
P C
PC
Department of Pharmacology, Monash University, Victoria, Australia.
Hodgson
W C
WC
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006973:Hypertension / Q000150:complications* / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D011450:Prostaglandin Endoperoxides, Synthetic / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012079:Renal Circulation / Q000187:drug effects*; D012701:Serotonin / Q000008:administration & dosage / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology
D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; D012701:Serotonin; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid