Importance of extracellular vesicles in hypertension.

Hypertension affects approximately 1.13 billion adults worldwide and is the leading global risk factor for cardiovascular, cerebrovascular, and kidney diseases. There is emerging evidence that extracellular vesicles participate in the development and progression of hypertension. Extracellular vesicles are membrane-enclosed structures released from nearly all types of eukaryotic cells. During their formation, extracellular vesicles incorporate various parent cell components, including proteins, lipids, and nucleic acids that can be transferred to recipient cells. Extracellular vesicles mediate cell-to-cell communication in a variety of physiological and pathophysiological processes. Therefore, studying the role of circulating and urinary extracellular vesicles in hypertension has the potential to identify novel noninvasive biomarkers and therapeutic targets of different hypertension phenotypes. This review discusses the classification and biogenesis of three EV subcategories (exosomes, microvesicles, and apoptotic bodies) and provides a summary of recent discoveries in the potential impact of extracellular vesicles on hypertension with a specific focus on their role in the blood pressure regulation by organs-artery and kidney, as well as renin-angiotensin-system.

Iodinated contrast media differentially affect afferent and efferent arteriolar tone and reactivity in mice: a possible explanation for reduced glomerular filtration rate.

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.

Angiotensin II type 2 receptor mediates sex differences in mice renal interlobar arteries response to angiotensin II.

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.