Suppression of the renin-angiotensin system induced by streptozotocin treatment in neonatal spontaneously hypertensive rats.
We studied whether or not neonatal streptozotocin (STZ) treatment would alter mean arterial pressure (MAP) and blood pressure regulating factors in conscious and unrestrained spontaneously hypertensive rats (SHR). Neonatal STZ administration to SHR resulted in type 2 diabetes mellitus with reduced MAP and heart rate. Plasma glucose was markedly increased in these diabetic animals and was inversely correlated with MAP. In the diabetic SHR, the hypotensive responses to captopril (SQ) or enalapril, administered intravenously, were diminished, regardless of preceding administrations of vasopressin V1-antagonist (AVPA) or hexamethonium (C6), when compared to findings in control rats. In contrast, the C6-induced hypotension was similar in rats with diabetes and control animals. AVPA led to no decrease in MAP in either group. Hypotensive responses to SQ following AVPA and C6 inversely correlated with the plasma levels of glucose in the diabetic group. The combined blockade of the renin-angiotensin system (RAS), sympathetic nervous system and vasoconstrictive action of vasopressin (AVP) abolished the differences in MAP between the groups. Pressor and bradycardic responses to intravenous noradrenaline, angiotensin II and AVP were practically identical in the diabetic and control SHR. Urinary aldosterone excretion rate was not altered by neonatal STZ treatment. In conclusion, a decrease in MAP in SHR with neonatal STZ treatment may be attributed to the suppressed pressor activity of RAS.
Takata
Y
Y
Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Yamashita
Y
Y
Takishita
S
S
Tomita
Y
Y
Tsuchihashi
T
T
Nakao
Y
Y
Iwase
M
M
Sadoshima
S
S
Fujishima
M
M
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D005730:Ganglionic Blockers / Q000494:pharmacology; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D006801:Humans; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013311:Streptozocin / Q000494:pharmacology*
D005730:Ganglionic Blockers; D006584:Hexamethonium Compounds; D000804:Angiotensin II; D001127:Arginine Vasopressin; D018738:Hexamethonium; D013311:Streptozocin; D002216:Captopril; D009638:Norepinephrine