TY - JOUR
T1 - Male gender predisposes to development of endotoxic shock in the rat
AU - Losonczy, Gy
AU - Kriston, T.
AU - Szabó, A.
AU - Müller, V.
AU - Harvey, J.
AU - Hamar, P.
AU - Heemann, U.
AU - Baylis, C.
N1 - Funding Information:
These studies were funded by NIH grant [HL 31933 (to CB), OTKA 025422, the Hungarian Kidney Foundation, the Research Funds of the Department of Pathophysiology of Semmelweis University Budapest (to GL), the Deutsche Akademische Austauschdienst (to UH) and the Oertel Stiftung (to AS and VM). The technical assistance of Glenn Keunzig, Kevin Engels, Lennie Sam-sell and Daisy Kertai are gratefully acknowledged.
PY - 2000/7
Y1 - 2000/7
N2 - Objective: After intravenous (i.v.) injection of lipopolysaccharide (LPS) macrophages release nitric oxide (NO) due to the expression of the inducible NO synthase (iNOS). After LPS NO is abundantly produced also in the cardiovascular system and may contribute to the development of hypotension and shock. Since the immune response, the synthesis of NO and the regulation of blood pressure (BP) differ between males and females, in the present study the effect of LPS on BP, renal function, the plasma and urinary concentration of the metabolites of NO as well as the splenic and aortic expression of the iNOS gene were compared between male and female rats. Methods: BP and renal function were measured in anesthetized rats following the i.v. injection of LPS (E. coli, 4 mg/kg). The NO2/- and NO3/- (metabolites of NO=NO(x)) concentration was measured by the Griess reaction. The iNOS gene expression was studied by RT-PCR. Results: Four hours after LPS, BP of males (n=9) was reduced by 63±12 mmHg versus 10±4 in females (n=7, P<0.005). Aminoguanidine, a selective inhibitor of iNOS, prevented the reduction of BP in males. The plasma concentration of NO(x) (P(NO(x)), μM) was lower in hypotensive males (128±20) than in normotensive females (235±29, P<0.005). Males also exhibited lower urinary NO(x) excretion (U(NO(x))V) after LPS (P<0.001 vs. females). Prior castration of males provided protection against hypotension (fall of BP: -4±4 mmHg, n=6, P<0.02 versus males) and resulted in higher P(NO(x)) as well as U(NO(x))V (both P<0.001 versus males and not different from females). Prior ovariectomy (n=5) had no influence on the hemodynamic and NO(x) response to LPS. Male rats displayed enhanced aortic iNOS/beta-actin ratio relative to females after LPS (n=3 in each group, P<0.05). Conclusions: (1) Male gender may sensitize to LPS-induced shock and (2) sensitivity of males to endotoxin is associated with an attenuated, not exaggerated total rate of NO synthesis. (C) 2000 Elsevier Science B.V.
AB - Objective: After intravenous (i.v.) injection of lipopolysaccharide (LPS) macrophages release nitric oxide (NO) due to the expression of the inducible NO synthase (iNOS). After LPS NO is abundantly produced also in the cardiovascular system and may contribute to the development of hypotension and shock. Since the immune response, the synthesis of NO and the regulation of blood pressure (BP) differ between males and females, in the present study the effect of LPS on BP, renal function, the plasma and urinary concentration of the metabolites of NO as well as the splenic and aortic expression of the iNOS gene were compared between male and female rats. Methods: BP and renal function were measured in anesthetized rats following the i.v. injection of LPS (E. coli, 4 mg/kg). The NO2/- and NO3/- (metabolites of NO=NO(x)) concentration was measured by the Griess reaction. The iNOS gene expression was studied by RT-PCR. Results: Four hours after LPS, BP of males (n=9) was reduced by 63±12 mmHg versus 10±4 in females (n=7, P<0.005). Aminoguanidine, a selective inhibitor of iNOS, prevented the reduction of BP in males. The plasma concentration of NO(x) (P(NO(x)), μM) was lower in hypotensive males (128±20) than in normotensive females (235±29, P<0.005). Males also exhibited lower urinary NO(x) excretion (U(NO(x))V) after LPS (P<0.001 vs. females). Prior castration of males provided protection against hypotension (fall of BP: -4±4 mmHg, n=6, P<0.02 versus males) and resulted in higher P(NO(x)) as well as U(NO(x))V (both P<0.001 versus males and not different from females). Prior ovariectomy (n=5) had no influence on the hemodynamic and NO(x) response to LPS. Male rats displayed enhanced aortic iNOS/beta-actin ratio relative to females after LPS (n=3 in each group, P<0.05). Conclusions: (1) Male gender may sensitize to LPS-induced shock and (2) sensitivity of males to endotoxin is associated with an attenuated, not exaggerated total rate of NO synthesis. (C) 2000 Elsevier Science B.V.
KW - Endotoxins
KW - Gender
KW - Nitric oxide
KW - Shock
UR - http://www.scopus.com/inward/record.url?scp=0034123659&partnerID=8YFLogxK
U2 - 10.1016/S0008-6363(00)00075-4
DO - 10.1016/S0008-6363(00)00075-4
M3 - Article
C2 - 10869545
AN - SCOPUS:0034123659
SN - 0008-6363
VL - 47
SP - 183
EP - 191
JO - Cardiovascular Research
JF - Cardiovascular Research
IS - 1
ER -