Inhibition of Ras-GTPase signaling by FPTIII ameliorates development of cardiovascular dysfunction in diabetic-hypertensive rats.
We studied the effect an inhibitor of Ras-GTPase (FPTIII, 1.5 mg/kg alt diem for 4 weeks) on mean arterial pressure (MAP), urine protein, vascular reactivity and cardiac function in streptozotocin (STZ)-induced diabetes in control normotensive (WKY) and spontaneously hypertensive rats (SHR). The increased urinary protein in STZ-treated WKY (D-WKY) and STZ-treated SHR (D-SHR) were significantly lower in FPTIII treated D-WKY and D-SHR. The abnormal vascular responsiveness to endothelin-1, angiotensin II, carbachol or histamine in isolated carotid artery from D-WKY and D-SHR was improved by chronic treatment with FPTIII. In isolated perfused hearts, recovery of left ventricular function from 40 min of global ischemia was significantly improved in FPTIII treated D-WKY and D-SHR. These results show that treatment with FPTIII can attenuate development of abnormal vascular reactivity and renal/cardiac dysfunction during simultaneous occurrence of hypertension and diabetes.
Yousif
Mariam H M
MH
Department of Pharmacology & Toxicology, Faculty of Medicine, Kuwait University, Kuwait. mariam@hsc.edu.kw
Benter
Ibrahim F
IF
Abul
Ahmed H T
AH
Abraham
Saju
S
Walther
Thomas
T
Akhtar
Saghir
S
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D002318:Cardiovascular Diseases / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D002339:Carotid Arteries / Q000187:drug effects / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications; D004357:Drug Synergism; D019332:Endothelin-1 / Q000494:pharmacology; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology; D006973:Hypertension / Q000150:complications; D066298:In Vitro Techniques; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D063065:Organophosphonates / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D015398:Signal Transduction / Q000187:drug effects*; D013311:Streptozocin; D018631:ras Proteins / Q000378:metabolism*
C436083:2-(2-oxo-2-((3,7,11-trimethyl-2,6,10-dodecatrienyl)oxy)aminoethyl)phosphonic acid, (2,2-dimethyl-1-oxopropoxy)methyl ester sodium; D019332:Endothelin-1; D063065:Organophosphonates; D000804:Angiotensin II; D013311:Streptozocin; D006632:Histamine; D002217:Carbachol; D020558:GTP Phosphohydrolases; D018631:ras Proteins