ABSTRACT
We tested the influence of estrogen on coronary resistance regulation by modulating nitric oxide (NO) and hydrogen peroxide (H2O2) levels in female rats. For this, estrogen levels were manipulated and the hearts were immediately excised and perfused at a constant flow using a Langendorff's apparatus. Higher estrogen levels were associated with a lower coronary resistance, increased nitric oxide bioavailability, and higher levels of H2O2. When oxide nitric synthase blockade by L-NAME was performed, no significant changes were found in coronary resistance of ovariectomized rats. Additionally, we found an inverse association between NO levels and catalase activity. Taken together, our data suggest that, in the absence of estrogen influence and, therefore, reduced NO bioavailability, coronary resistance regulation seems to be more dependent on the H2O2 that is maintained at low levels by increased catalase activity.
Subject(s)
Catalase/metabolism , Coronary Vessels/enzymology , Coronary Vessels/pathology , Estrogens/pharmacology , Hydrogen Peroxide/metabolism , Nitric Oxide/metabolism , Animals , Antioxidants/metabolism , Body Weight/drug effects , Coronary Vessels/drug effects , Female , In Vitro Techniques , Myocardial Contraction/drug effects , Myocardium/enzymology , Myocardium/pathology , Nitrates/metabolism , Nitrites/metabolism , Perfusion , Pressure , Rats , Rats, WistarABSTRACT
PURPOSE: To determine the effect of the iodinated contrast medium iodixanol on arteriolar tone in afferent and efferent arterioles of the glomerulus and the functional interactions with the major modulators of arteriolar tone, angiotensin II and nitric oxide, in mice. MATERIALS AND METHODS: Animal handling conformed to the ethics guidelines of the Office for Health and Social Matters of Berlin. Arterioles were isolated from 136 C57BL/6 mice, perfused with either vehicle solution or iodixanol (23 mg of iodine per milliliter) for 20 minutes, followed by angiotensin II administration. Fluorescence of 3-amino-4-(N-methylamino)-2',7'-difluorofluorescein (DAF-FM) and dihydroethidium (DHE) were used for quantification of nitric oxide bioavailability and superoxide concentration, respectively. Statistical analysis of time- and dose-dependent data was performed by using the nonparametric test for repeated measurements. RESULTS: With iodixanol, afferent arteriole diameters were significantly reduced from 9.2 µm to 8.3 µm; in control group, the diameters were increased from 8.7 µm to 9.3 µm (P = .008). Nitric oxide synthase inhibition augmented iodixanol-induced constriction, with diameters reduced from 9.9 µm to 5.8 µm (P < .0001). DAF-FM fluorescence increased less during iodixanol treatment and nitric oxide synthase inhibition (3.6% and 3.7% vs 10.7% in control group, P = .009 and P = .049, respectively), indicating impaired nitric oxide bioavailability. With iodixanol, DHE fluorescence ratio was increased by 12% (P < .0001). Angiotensin II responses were enhanced by iodixanol and by nitric oxide synthase inhibition after perfusion with iodixanol (3.3 µm and 4.3 µm vs 7.5 µm [control group] with 1 × 10(-6)/mol/L angiotensin II, P = .03 for both). In contrast, in efferent arterioles, neither their basal diameters nor the responses to angiotensin II were significantly affected by iodixanol. CONCLUSION: A more pronounced effect of iodixanol on afferent than on efferent arterioles may contribute to the reduction of glomerular filtration rate in contrast medium-induced acute kidney injury. Decreased nitric oxide bioavailability and increased concentration of superoxide explain the increased tone and reactivity in afferent arterioles perfused with iodixanol.
Subject(s)
Arterioles/drug effects , Contrast Media/pharmacology , Glomerular Filtration Rate/drug effects , Triiodobenzoic Acids/pharmacology , Analysis of Variance , Angiotensin II/pharmacology , Animals , Cyclic N-Oxides/pharmacology , Dicarbethoxydihydrocollidine/analogs & derivatives , Dicarbethoxydihydrocollidine/pharmacology , Ethylamines/pharmacology , Fluoresceins/pharmacology , Kidney Glomerulus/drug effects , Male , Mice , Mice, Inbred C57BL , NG-Nitroarginine Methyl Ester/pharmacology , Nitric Oxide/metabolism , Spin Labels , Statistics, Nonparametric , Superoxides/metabolism , Vasoconstriction/drug effectsABSTRACT
OBJECTIVE: Functional sex differences are described in several vascular beds. In the case of renal vessels, sex differences could influence processes like regulation of blood pressure and ion balance. Angiotensin II and nitric oxide are important regulators of renal vascular tone. Females have higher nitric oxide synthase expression, nitric oxide bioavailability and ratio of angiotensin II type 2/type 1 receptors. Thus, our objective was to examine whether renal interlobar arteries present sex differences in their response to angiotensin II, and whether angiotensin II type 2 receptors play a role in such differences. METHODS: We investigated the isometric contraction and relaxation of interlobar arteries from female and male mice under blockade of nitric oxide synthases and angiotensin II type 2 receptors. We also investigated the expression of angiotensin II receptors (type 1 and 2) and endothelial nitric oxide synthase. RESULTS: Significantly less intense contraction to angiotensin II were seen in arteries from females in comparison to male mice. Inhibition of nitric oxide synthases and endothelial removal abolished this difference. Angiotensin II type 2 receptors blockade enhanced contraction to angiotensin II in females, but not in males. Endothelial-dependent vasodilation was more dependent on nitric oxide in females than in males. Expression of angiotensin II type 1 and type 2 receptors was similar between sexes. Expression of endothelial nitric oxide synthase was higher in females. CONCLUSION: A sex-specific, nitric oxide-mediated effect via angiotensin II type 2 receptors underlies the sex differences in the response of interlobar arteries to angiotensin II. Our findings may help understanding sex differences in renal hemodynamics and blood pressure control.
