Study on six-minute walk test and cardiac output response against exercise in patients with chronic heart failure / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the significance of cardiac output (CO) response against exercise determined by IGR method and LVEF, 6 MWT distance in patients with chronic heart failure (CHF).</p><p><b>METHOD</b>To adopt 6 MWT, and before and after the test measuring the CO by the IGR method, furthermore, measure LVEF to 36 patients (heart failure group) with CHF, compare with the health groups (control group).</p><p><b>RESULTS</b>The 6MWT distance of heart failure group (333.00 +/- 49.64) m decrease compared with the control group (582.56 +/- 67.97) m (P < 0.01), moreover, the distance of NYHA class III (314.82 +/- 36.27) m is significantly shorter than II (361.57 +/- 55.42) m (P < 0.05). The LVEF of heart failure group (47.0 +/- 0.4)% reduce compared with the control group (66.9 +/- 5.2)% (P < 0.01), and the data of NYHA class III (43.3 +/- 10.3)% is significantly lower than II (52.8 +/- 7.6)% (P < 0.01). The increase in CO response against exercise of heart failure group (5.97 +/- 1.89) L/min decrease compared with control group (8.88 +/- 0.52) L/min (P < 0.01), furthermore, the value of NYHA class III (5.31 +/- 1.52) L/min, compared with II (7.01 +/- 1.98)L/min, is obviously lower (P < 0.01). The 6MWT distance correlates positively with the increase in CO response against exercise (r = 0.63, P < 0.01), but the correlation is not found between the increase CO response against exercise and the LVEF (r = 0.11, P > 0.05).</p><p><b>CONCLUSION</b>Our results show that CO response against exercise measured by IGR method, with the advantages of being noninvasive, safe, convenient and accurate, combining with the 6MWT can evaluate cardiac reserve in patient with CHF.</p>

Effect of Insulin on D_5 Dopamine Receptor Expression and Function in Renal Proximal Tubule Cells / 中华高血压杂志

Objective To investigate the effect of insulin on D_5 dopamine receptor expression and function in renal proximal tubule (RPT).Methods Immortalized RPT cells and D_5 receptor transfected HEK293 (HEK-D_5) cells were used in the study to investigate the effect of insulin on D_5 receptor expression and function,and those effects were compared in RPT cells from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). The function of D_5 receptor was determined by measurement of the Na~+-K~+-ATPase activity in HEK-D_5 cells. Results Insulin increased D_5 receptor protein expression in a concentration and time-dependent manner in WKY RPT cells,but not in SHR.The basal level of D_5 receptor expression was higher in WKY cells than that in SHR cells. Stimulation with fenoldopam(D_1-like dopamine receptor agonist) inhibited the Na~+-K~+-ATPase activity;pretreat- ment with insulin increased the inhibitory effect of fenoldopam on Na~+-K~+-ATPase activity in HEK-D_5 cells. Conclusion The abnormal regulation of insulin on D_5 receptor expression and function might be involved in the path- ogenesis of essential hypertension.

G protein kinase 4gammaA142V overexpression induced hypertension by downregulating D1 receptors in transgenic mice / 中华心血管病杂志

<p><b>OBJECTIVE</b>Abnormalities in dopamine production and receptor function have been described in human essential hypertension and rodent models of genetic hypertension. We investigated the role of G protein kinase (GRK) 4gamma in essential hypertension in GRK4gamma mutant A142V transgenic mice.</p><p><b>METHODS</b>Blood pressure, renal sodium excretion, D(1) receptor protein expression and phosphorylation were measured in GRK4gammaA142V transgenic mice and control mice. Moreover, the effects of GRK4 inhibition by antisense oligonucleotides on D(1) receptor expressions were determined in HK-2 cells.</p><p><b>RESULTS</b>As compared with their control mice, GRK4gammaA142V transgenic mice had higher blood pressure, lower D(1) receptor expression (0.6 +/- 0.2 vs. 1.5 +/- 0.2, P < 0.05), higher D(1) receptor phosphorylation [(65 +/- 7) DU vs. (35 +/- 7) DU, P < 0.05] in renal cortical membranes and the diuretic and natriuretic effects after stimulation of renal D(1) receptor were impaired in GRK4gammaA142V transgenic mice. Inhibition of GRK4 expression (0.60 +/- 0.10 vs. 1.30 +/- 0.09, P < 0.05) by GRK4 antisense oligonucleotides upregulated D(1) receptor expression (1.5 +/- 0.2 vs. 0.8 +/- 0.1, P < 0.05) in HK-2 cells.</p><p><b>CONCLUSIONS</b>Our results show that GRK4gammaA142V overexpression induced hypertension is mediated by dowregulated renal D(1) receptor expressions in GRK4gammaA142V transgenic mice.</p>

Hypertension in D3 dopamine receptor deficient mice / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the mechanisms by which hypertension occurs in D(3) dopamine receptor null mice (D(3)-/-).</p><p><b>METHODS</b>Several parameters, including blood pressure, renal sodium excretion, D(3) receptor protein and mRNA expression, plasma renin activity, norepinephrine concentration and AT(1) receptor expression were checked in D(3)-/- mice and their littermate wild type mice (D(3)+/+). Moreover, the vasorelaxant effect of D(3) receptor stimulation was measured with ex-vivo mesenteric artery isolated from Wistar-Kyoto rats.</p><p><b>RESULTS</b>Blood pressure was higher in D(3)-/- mice compared with that in D(3)+/+ mice, salt-loading had no effect on blood pressure in both groups, at the last period, sodium excretion was lower in D(3)-/- mice as compared with D(3)+/+ mice, renal renin activity and AT(1) receptor expression were higher in D(3) -/- [corrected] mice than in D(3) +/+ [corrected] mice. In contrast, no difference of renal norepinephrine was found in two groups. When using angiotensin II subtype-1 receptor antagonist, the systolic blood pressure declined for a longer duration in mutant mice than in wild-type mice. Vaso-relaxation was found in ex-vivo isolated mesenteric artery when D(3) receptor was stimulated.</p><p><b>CONCLUSIONS</b>Elevation of blood pressure in D(3)-/- mice might be related with impaired renal sodium excretion and vaso-relaxation in resistance artery.</p>