Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q9UID3 (FFR)
 233 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin resistance and compensatory hyperinsulinemia often coexist in hypertensive patients, which may play a role in the development of hypertension. Because medullary blood flow (MBF), which is strongly influenced by the nitric oxide (NO) system, is thought to be an important component of blood pressure and sodium balance, we focused particularly on MBF in fructose-induced hypertensive rats. Moreover, it has been reported that the increased reactive oxygen species (ROS) in the kidney may contribute to the development of hypertension. Our study was thus designed to test the hypotheses that MBF is diminished in fructose-hypertensive rats (FFR) and that administration of tempol, a membrane-permeable mimetic of superoxide dismutase (SOD), decreases mean arterial pressure (MAP) by increasing MBF. Male Sprague-Dawley rats (180 to 200 g) were divided into 6 groups: control untreated (C, n = 5), control tempol-treated (in drinking water) (CT, n = 4), control L-arginine-treated (in drinking water) (CA, n = 6), fructose-fed untreated (F, n = 7), fructose-fed tempol-treated (FT, n = 7), and fructose-fed L-arginine-treated rats (in drinking water) (FA, n = 6). MAP and 24-hour urine samples were measured weekly over a 4-week test period. Changes in MBF, cortical blood flow (CBF), and renal blood flow (RBF) were determined by implanted optical fiber-, laser- and pulse-Doppler flow measurement techniques 4 weeks after starting the diet. Fructose feeding resulted in hyperinsulinemia, significantly elevated MAP, decreased MBF without changes in RBF or CBF, and decreased sodium excretion in the F group compared to the C group. Administration of tempol significantly decreased MAP and plasma insulin in contrast to increased MBF and sodium excretion in the FT group compared to those in the F group. Results indicated that MBF played an important role in the development of hypertension in the F group. Impairment of renal medullary NO systems may induce sustained elevation of blood pressure and retention of sodium in fructose-fed rats. The decrease in MAP with an increase of MBF in the FT group is consistent with the hypothesis that tempol increases the level of NO available to influence mechanisms involved in the control of MBF.
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PMID:Superoxide dismustase mimetic tempol decreases blood pressure by increasing renal medullary blood flow in hyperinsulinemic-hypertensive rats. 1537 86

The normally positive force- and Ca2+ -frequency responses (FFR and CaFR) are inverted in heart failure (HF); whether oxidative stress contributes to these abnormalities is unknown. We evaluated the impact of acute and prolonged oxidative stress on contraction and Ca2+ handling in adult rat cardiomyocytes. Acute (30 min) exposure to H2O2 (100 microM) induced a twofold increase (P<0.025) in intracellular oxyradicals together with contractile depression despite preservation of the Ca2+ transient and the FFR and CaFR to 3 Hz, indicating reduced myofilament Ca2+ responsiveness. In contrast, prolonged (24 h) exposure to the copper-zinc superoxide dismutase inhibitor diethyldithiocarbamic acid (DDC, 1 microM) similarly augmented oxyradicals but also increased cell size, and contraction and Ca2+ transient duration (P<0.025). DDC-treated myocytes displayed inverted FFRs and attenuated (though still positive) CaFRs as compared to control, indicating reduced myofilament Ca2+ responsiveness coupled with altered Ca2+ handling. Protein levels of the Na+ -Ca2+ exchanger (NCX), sarcoplasmic reticular (SR) Ca2+ ATPase (SERCA2), and serine-16 phosphorylated phospholamban (pSer16-PLB) were increased (P<0.025), whereas dihydropyridine receptor abundance was decreased. Total PLB and ryanodine receptor protein expression were unchanged. Caffeine-induced Ca2+ release showed increased NCX activity (P<0.025) without changes in total releasable SR Ca2+, suggesting compensatory changes in SERCA2 and pSer16-PLB to maintain SR Ca2+ load. The superoxide scavenger Tiron attenuated these effects. Thus, acute oxyradical exposure rapidly depresses myofibrillar Ca2+ responsiveness. Prolonged oxidative stress further induces alterations in Ca2+ handling that combined with extant reductions in myofibrillar responsiveness invert the FFR. With regard to Ca2+ handling, reduced transsarcolemmal Ca2+ flux rather than reduced SR Ca2+ uptake was the primary determinant of a negative FFR. Analogous changes may be operative in HF, a state characterized by both oxidative stress and Ca2+ dysregulation.
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PMID:Prolonged oxidative stress inverts the cardiac force-frequency relation: role of altered calcium handling and myofilament calcium responsiveness. 1628 76