761 ASSOCIATION OF E/Ea AND NT-proBNP WITH RENAL FUNCTION IN PATIENTS WITH ESSENTIAL HYPERTENSION

Background: To evaluate the association of left ventricular (LV) diastolic function and N-terminal pro-brain natriuretic peptide (NT-proBNP) with renal function in essential hypertension. Methods: In 406 hypertensive patients(mean age, 59±13 years), LV diastolic function was measured by the ratio of early diastolic transmitral E wave velocities to tissue Doppler mitral annulus early diastolic Ea wave velocities (E/Ea) and NT-proBNP was determined. The subjects were classified into three groups: E/Ea⩽10 group(n = 85), 10 < E/Ea⩽15 group(n = 230) and E/Ea>15 group(n = 91). The renal function was estimated by glomerular filtration rate (GFR) with 99mTc-DTPA. GFR from 30 to 59 ml/min/1.73m2 was defined as Stage 3 CKD. Urinary albumin/creatinine ratio (UACR) served to determine albuminuria. Results: GFR and UACR was significantly correlated with E/Ea and NT-proBNP (P < 0.0001). GFR was lower and UACR was higher in E/Ea⩽15 group than in 10 < E/Ea⩽15 group or E/Ea⩽10 group(P < 0.0001). GFR had significant correlation with age, gender, E/Ea, lgNT-proBNP and lgUACR in multivariate analysis. Patients with higher NT-proBNP were characterized by poorer renal function, while GFR was even lower in patients of LV diastolic dysfunction with higher NT-proBNP. Patients with Stage 3 CKD could be detected by an elevation of NT-proBNP at a cut-off point of 103pg/ml or by increased E/Ea at a cut-off point of 12.4. Conclusions: LV diastolic function, assessed with E/Ea and NT-proBNP is associated with renal function in essential hypertension.


Methods
In 406 hypertensive patients(mean age, 59 Ϯ 13 years), LV diastolic function was measured by the ratio of early diastolic transmitral E wave velocities to tissue Doppler mitral annulus early diastolic Ea wave velocities (E/Ea) and NT-proBNP was determined. The subjects were classifi ed into three groups: E/Ea Յ 10 group(n ϭ 85), 10 Ͻ E/Ea Յ 15 group(n ϭ 230) and E/Ea Ͼ 15 group(n ϭ 91). The renal function was estimated by glomerular fi ltration rate (GFR) with 99m Tc-DTPA. GFR from 30 to 59ml/min/1.73m 2 was defi ned as Stage 3 CKD. Urinary albumin/creatinine ratio (UACR) served to determine albuminuria.
Results GFR and UACR was signifi cantly correlated with E/Ea and NT-proBNP (P Ͻ 0.0001). GFR was lower and UACR was higher in E/Ea Յ 15 group than in 10 Ͻ E/Ea Յ 15 group or E/Ea Յ 10 group(P Ͻ 0.0001). GFR had signifi cant correlation with age, gender, E/Ea, lgNT-proBNP and lgUACR in multivariate analysis. Patients with higher NT-proBNP were characterized by poorer renal function, while GFR was even lower in patients of LV diastolic dysfunction with higher NT-proBNP. Patients with Stage 3 CKD could be detected by an elevation of NT-proBNP at a cut-off point of 103pg/ml or by increased E/Ea at a cut-off point of 12.4.
Conclusions LV diastolic function, assessed with E/Ea and NT-proBNP is associated with renal function in essential hypertension.

ACTIVATION OF D4 DOPAMINE RECEPTOR DECREASES AT1 ANGIOTENSIN II RECEPTOR EXPRESSION IN RAT RENAL PROXIMAL TUBULE CELLS
Kun Deng 1,2 , Xiaoyan Wang* 3 , Duofen He 1,2 , Yu Han 1,2 , Laureano D. Background The dopaminergic and renin angiotensin systems interact to regulate blood pressure. Disruption of the D 4 dopamine receptor gene in mice produces hypertension that is associated with increased renal AT 1 receptor expression. We hypothesize that D 4 receptor can inhibit AT 1 receptor expression and function in renal proximal tubules (RPTs) cells from Wistar-Kyoto (WKY) rats, the regulation of D 4 receptor on AT 1 receptor is aberrant in RPT cells from spontaneously hypertensive rats (SHRs).

Methods And Results
The D 4 receptor agonist, PD168077, decreased AT 1 receptor protein expression in WKY RPT cells but increased the receptor expression in SHR RPT cells. The inhibitory effect of D 4 receptor on AT 1 receptor expression in WKY RPT cells was blocked by a calcium channel blocker, nicardipine or calcium free medium. Angiotensin II increased Na 1 -K 1 ATPase activity in WKY cells. Pretreatment with PD168077 decreased the stimulatory effects of angiotensin II on Na 1 -K 1 ATPase activity in WKY cells. However, in SHR cells, the inhibitory effect of D 4 receptor on angiotensin II-mediated Na 1 -K 1 ATPase activity was aberrant; pretreatment with PD168077 augmented the stimulatory effect of AT 1 receptor on Na 1 -K 1 ATPase activity in SHR cells. We also infused angiotensin II via renal artery, found sodium excretion decrease, while in the pre-infusion with PD168077, the inhibitory effect of Ang II on sodium excretion was decreased in WKY rats, increased in SHRs.

Conclusions
We suggest that a differential interaction between D4 and AT1 receptors may play a role in the differential regulation of sodium excretion and blood pressure in hypertension.

Methods And Results
The effect of D 1 -like receptor on renalase expression and function was checked in immortalized renal proximal tubule (RPT) cells from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). It resulted that D 1 -like receptor agonist, fenoldopam increased renalase protein expression and function in WKY RPT cells, but decreased it in SHR cells. These effects were blocked by D 1 -like receptor antagonist SCH 23390. Fenoldopam increased renalase mRNA level in WKY RPT cells, but not in SHR cells. Fenoldopam increased the degradation of renalase protein in both WKY and SHR cells. However, the degradation degree was higher in SHR cells than in WKY cells. The regulation of D 1 -like receptor on renalase was mainly via D 5 receptor, because D5 antisense blocked inhibitory effect of D 1 -like receptor on renalase in WKY cells. Moreover, PKC inhibitor 19-31 blocked the effect of fenoldopam on renalase expression; PKC agonist (PMA) inhibited renalase expression and function. Consistent with the in-vitro study, renalase expression was lower in kidney from SHRs than in WKY rats.