Role of endothelin-1 and thromboxane A2 in renal vasoconstriction induced by angiotensin II in diabetes and hypertension.
BACKGROUND
Interactions among angiotensin II (Ang II), endothelin-1 (ET-1) and thromboxane A2 (TXA2) may play an important role in the regulation of renal function. The present study investigated the participation of TXA2 and ET-1 in the increase in renal vascular resistances (RVR) induced by Ang II, as well as the consequences of diabetes, hypertension, and the combination of both on this response.


METHODS
Isolated kidneys from male normoglycemic or streptozotocin-induced diabetic Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were used. The increase in perfusion pressure (PP) produced by Ang II was studied in the absence or presence of the TXA2 receptor antagonist, ifetroban, or the ETA/ETB receptor antagonist, PD145065.


RESULTS
Systolic arterial pressure (SAP) was higher in SHR than in WKY, but diabetic rats (D) from each strain showed lower SAP values than their respective non-diabetic rats. Basal renal PP was higher in WKY and SHR than in WKY-D and SHR-D. Increases in renal PP produced by Ang II were comparable in the kidneys from all groups. Either ifetroban or PD145065 reduced the maximal Ang II response in all animals. The maximal inhibitory effect of ifetroban was higher (P<0.05) in WKY than in the other groups. However, the maximal inhibitory effect of PD145065 was lower in SHR than in the other groups.


CONCLUSIONS
This study supports a role for ET-1 and TXA2 as mediators of the increase in renal vascular resistance produced by Ang II. These results indicate that the participation of ET-1 in the renal vasoconstriction produced by Ang II was reduced under hypertensive conditions, and that of TXA2 was reduced by both diabetes and hypertension.
Cediel
Eva
E
Department of Pharmacology FES-Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, México.
Vázquez-Cruz
Beatriz
B
Navarro-Cid
Josefa
J
de las Heras
Natalia
N
Sanz-Rosa
David
D
Cachofeiro
Victoria
V
Lahera
Vicente
V
D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism*; D006973:Hypertension / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D007668:Kidney / Q000098:blood supply*; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D010080:Oxazoles / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017466:Receptors, Endothelin / Q000378:metabolism; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D012079:Renal Circulation / Q000187:drug effects; D013928:Thromboxane A2 / Q000378:metabolism*; D014655:Vascular Resistance; D014661:Vasoconstriction / Q000187:drug effects
D019086:Bridged Bicyclo Compounds, Heterocyclic; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D009842:Oligopeptides; D010080:Oxazoles; D017466:Receptors, Endothelin; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D000804:Angiotensin II; C082887:PD 145065; D013928:Thromboxane A2; C078904:ifetroban