Objective::Dopamine, via its receptors, plays a vital role in the maintenance of blood pressure by modulating renal sodium transport. However, the role of the D 4 dopamine receptor (D 4 receptor) in renal proximal tubules (PRTs) is still unclear. This study aimed to verify the hypothesis that activation of D 4 receptor directly inhibits the activity of the Na +-K +-ATPase (NKA) in RPT cells. Methods::NKA activity, nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) levels were measured in RPT cells treated with the D 4 receptor agonist PD168077 and/or the D 4 receptor antagonist L745870, the NO synthase inhibitor NG-nitro-L-arginine-methyl ester (L-NAME) or the soluble guanylyl cyclase inhibitor 1H-[1,2,4] oxadiazolo-[4,3-a] quinoxalin-1-one (ODQ). Total D 4 receptor expression and its expression in the plasma membrane were investigated by immunoblotting in RPT cells from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). Results::Activation of D 4 receptors with PD168077, inhibited NKA activity in RPT cells from WKY rats in a concentration- and time-dependent manner. The inhibitory effect of PD168077 on NKA activity was prevented by the addition of the D 4 receptor antagonist L745870, which by itself had no effect. The NO synthase inhibitor L-NAME and the soluble guanylyl cyclase inhibitor ODQ, which by themselves had no effect on NKA activity, eliminated the inhibitory effect of PD168077 on NKA activity. Activation of D 4 receptors also increased NO levels in the culture medium and cGMP levels in RPT cells. However, the inhibitory effect of D 4 receptors on NKA activity was absent in RPT cells from SHRs, which could be related to decreased plasma membrane expression of D 4 receptors in SHR RPT cells. Conclusions::Activation of D 4 receptors directly inhibits NKA activity via the NO/cGMP signaling pathway in RPT cells from WKY rats but not SHRs. Aberrant regulation of NKA activity in RPT cells may be involved in the pathogenesis of hypertension.

Objective::Dopamine, via its receptors, plays a vital role in the maintenance of blood pressure by modulating renal sodium transport. However, the role of the D 4 dopamine receptor (D 4 receptor) in renal proximal tubules (PRTs) is still unclear. This study aimed to verify the hypothesis that activation of D 4 receptor directly inhibits the activity of the Na +-K +-ATPase (NKA) in RPT cells. Methods::NKA activity, nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) levels were measured in RPT cells treated with the D 4 receptor agonist PD168077 and/or the D 4 receptor antagonist L745870, the NO synthase inhibitor NG-nitro-L-arginine-methyl ester (L-NAME) or the soluble guanylyl cyclase inhibitor 1H-[1,2,4] oxadiazolo-[4,3-a] quinoxalin-1-one (ODQ). Total D 4 receptor expression and its expression in the plasma membrane were investigated by immunoblotting in RPT cells from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). Results::Activation of D 4 receptors with PD168077, inhibited NKA activity in RPT cells from WKY rats in a concentration- and time-dependent manner. The inhibitory effect of PD168077 on NKA activity was prevented by the addition of the D 4 receptor antagonist L745870, which by itself had no effect. The NO synthase inhibitor L-NAME and the soluble guanylyl cyclase inhibitor ODQ, which by themselves had no effect on NKA activity, eliminated the inhibitory effect of PD168077 on NKA activity. Activation of D 4 receptors also increased NO levels in the culture medium and cGMP levels in RPT cells. However, the inhibitory effect of D 4 receptors on NKA activity was absent in RPT cells from SHRs, which could be related to decreased plasma membrane expression of D 4 receptors in SHR RPT cells. Conclusions::Activation of D 4 receptors directly inhibits NKA activity via the NO/cGMP signaling pathway in RPT cells from WKY rats but not SHRs. Aberrant regulation of NKA activity in RPT cells may be involved in the pathogenesis of hypertension.

Objective To study the effect of human G-coupled protein kinase 4(GRK4) A142V overexpression on angiotensin Ⅱ1 type(AT1 ) receptor and its-mediated proliferation of rat vascular smooth muscle cells .Methods We constructed a lentiviral vec-tor carrying human GRK4-EGFP gene and observed its expression in A10 cells .Expression of AT1 receptor were determined by im-munoblotting ,GRK4 activity were checked by spectrophotometry ;the linkage between GRK4 and AT1 receptor were determined by co-immunoprecipitation .[3 H] thymidine incorporation was used to detect changes of cell proliferation .Results As compared with the control cells ,A142V-transfected cells had higher GRK4 activity and higher AT1 receptor expression ;there was linkage between GRK4 and AT1 receptor ,the co-immunoprecipitation levels were lower in A142V cells .The basal levels of VSMC proliferation was higher in A142V cells ,Ang Ⅱ increased VSMC proliferation to a greater extent in A 142V cells .Conclusion GRK4 A142V ,via in-creasing GRK4 activity ,increases AT1 receptor expression and function in vascular smooth muscle cell proliferation .

AIM: To explore the effect of endoplasmic reticulum stress on cardiac myocyte apoptosis in mouse congestive heart failure induced by myocardial infraction.METHODS: The mouse model of heart failure was established by ligating the left anterior descending coronary to produce acute myocardial infarction.Thirty-two mice were divided into 4 groups: sham group and groups of post-operation at time points of 2,4 or 6 weeks,respectively.The ventricular dilatation and left ventricular functions were assessed by echocardiography.The expression of GRP78,CHOP,caspase-12,cleaved caspase-12,JNK and phosphorylated-JNK was detected by Western blotting.The cardiac myocyte apoptosis was determined by terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling(TUNEL).RESULTS: The cardiac expression of endoplasmic reticulum chaperones GRP78 was significantly increased in the hearts with functional failure.The upregulated expression of CHOP,phosphorylated-JNK and cleaved caspase-12 illuminated that the CHOP-JNK-caspase-12 dependent pathways for endoplasmic reticulum-initiated apoptosis were activated in the heart with functional failure by myocardial infraction.CONCLUSION: These findings suggest that the congestive heart failure induced by myocardial infraction is associated with endoplasmic reticulum stress and activation of CHOP,JNK,caspase-12 dependent pathways for endoplasmic reticulum-initiated apoptosis.