Diabetes impairs the atrial natriuretic peptide relaxant action mediated by potassium channels and prostacyclin in the rabbit renal artery.
Diabetes is associated with increased prevalence of hypertension, cardiovascular and renal disease. Atrial natriuretic peptide (ANP) plays an important role in cardiovascular pathophysiology and is claimed to have cardioprotective and renoprotective effect in diabetic patients. The working hypothesis was that alloxan-induced diabetes might modify the vascular effects of ANP in isolated rabbit renal arteries and the mechanisms involved in such actions. Plasma ANP levels were higher in diabetic rabbits than in control rabbits. ANP (10(-12)-10(-7)M) induced a relaxation of precontracted renal arteries, which was lower in diabetic than in control rabbits. In arteries from both groups of animals, endothelium removal decreased the ANP-induced relaxation but inhibition of NO-synthesis did not modify ANP-induced relaxations. In KCl-depolarised arteries, relaxation to ANP was almost abolished both in control and diabetic rabbits. Tetraethylammonium (TEA) partly inhibited the relaxation to ANP in control rabbits but did not modify it in diabetic rabbits. Glibenclamide and 4-aminopyridine inhibited the relaxation to ANP, and these inhibitions were lower in diabetic than in control rabbits. Indomethacin potentiated the relaxation to ANP, more in control than in diabetic rabbits. In the presence of ANP the renal artery released thromboxane A(2) and prostacyclin, and the release of prostacyclin resulted decreased in diabetic rabbits. The present results suggest that diabetes produces hyporeactivity of the rabbit renal artery to ANP by mechanisms that at least include the reduced modulation by prostacyclin and a lower participation of ATP-sensitive K(+) channel (K(ATP)), voltage-sensitive K(+) channels (K(V)) and TEA-sensitive K(+) channels (K(Ca)).
Departamento de Fisiología, Universidad de Valencia, Valencia, Spain.
Vannina G
VG
Marrachelli
José M
JM
Centeno
Ignacio
I
Miranda
María
M
Castelló-Ruiz
María C
MC
Burguete
Teresa
T
Jover-Mengual
Juan B
JB
Salom
Germán
G
Torregrosa
Francisco J
FJ
Miranda
Enrique
E
Alborch
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000502:physiology; D011464:Epoprostenol / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D015221:Potassium Channels / Q000502:physiology; D011817:Rabbits; D012077:Renal Artery / Q000187:drug effects* / Q000502:physiology; D019789:Tetraethylammonium / Q000494:pharmacology; D013928:Thromboxane A2 / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D015221:Potassium Channels; D013928:Thromboxane A2; D019789:Tetraethylammonium; D009320:Atrial Natriuretic Factor; D011464:Epoprostenol