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Recently, we reported that the blunted natriuretic ability related to an attenuation of renal dopaminergic activity might play an important role in the hypertensive mechanisms of overweight patients with essential hypertension. On the other hand, the interrelationships between obesity, blood pressure and renal sodium handling in normotensives (NT) have not been clear. The purpose of the present study is to reveal the role of renal dopaminergic activity on renal sodium handling in overweight NT. The study consisted of 52 hospitalized NT receiving a regular diet containing 200mEq of sodium, 75mEq of potassium, 2400kcal/day, who were divided into two groups of 31 non-obese (NNT) and 21 obese (ONT) subjects. NNT was categorized as the body mass index (BMI) less than, and ONT as the BMI equal to or more than, 25kg/m2. In the early morning, after overnight fasting, all subjects remained in a supine state and were examined for renal clearance. During the clearance period, mean arterial pressure (MAP), heart rate (HR), endogenous creatinine clearance (Ccr), urinary excretion of sodium (UNaV), fractional excretion of sodium (FENa) and of inorganic phosphorus (FEP) and urinary excretion of free dopamine (uDA) were determined. There were no significant differences in age, HR, Ccr or UNaV between the two groups. Higher MAP and lower FENa) were observed in ONT than in NNT, but the differences in these parameters were not statistically significant. However, FENa in ONT was significantly lower than in MAP-and Ccr-matched NNT. In addition, FENa correlated negatively with BMI in ONT, unlike in NNT. MAP was correlated positively with FENa, and a similar tendency was found between MAP and FEP in NNT, but not in ONT. On the other hand, there was no significant correlation between BMI and uDA in either NNT or ONT. This result was different from our previous data in patients with essential hypertension (EHT) in which BMI correlated with uDA positively in non-obese EHT and negatively in obese EHT. These findings suggest that blunted natriuretic ability may exist in ONT, and the role of renal dopaminergic activity related to the attenuated natriuretic ability in ONT may be less important than in obese EHT.

Studies were conducted to evaluate the role of water-sodium balance and renal dopaminergic activity in the hypertensive mechanisms of overweight patients with essential hypertension (EHT). The body mass index (BMI) was correlated positively with arterial pressure, plasma volume, extracellular fluid volume, or total exchangeable sodium and negatively with plasma noradrenaline concentration or plasma renin activity in patients with EHT. Fractional excretion of sodium (FENa) was significantly lower in overweight patients with EHT than that in normal-weight patients with EHT. Hypotensive effects of sodium restriction or the natriuretic response to infused dopamine was more remarkable in overweight than in normal-weight patients with EHT. Urinary excretion of free dopamine (UDA) was correlated positively with simultaneously measured urinary excretion of sodium or FENa and negatively with the natriuretic response to dopamine infusion. In addition, UDA was positively correlated with the BMI in normal-weight patients with EHT, whereas the relation between UDA and BMI was significantly negative in overweight patients with EHT. These findings suggest that the expansion of body fluid volume and sodium might result from the blunted natriuretic ability due to an attenuation of the renal dopaminergic activity in overweight patients with EHT. The expansion of body fluid volume and sodium may play an important role in the hypertensive mechanisms of overweight patients with EHT.

Our previous studies have shown that a suppressed pressure natriuresis may contribute to the hypertensive mechanism in patients with essential hypertension (EHT), particularly in low renin patients (LRH). In this study, in order to clarify the role of renal dopaminergic activity in the blunted natriuresis of LRH, the conversion of 1-dopa (DOPA) to dopamine (DA) in the kidneys was investigated in 9 normotensive subjects (NT) and 20 EHT, including 15 normal renin EHT (NRH) and 5 LRH. All subjects were hospitalized and received a constant diet (Na:120mEq, K:75mEq daily). Plasma DOPA concentration (p-DOPA:HPLC-ECD), creatinine clearance (Ccr), urinary excretion of sodium (UNaV) and DA (UDA), as well as fractional excretion of sodium (FENa) were measured before and after the single oral administration of 1-DOPA (400mg). DOPA administration caused a significant increase of p-DOPA, UDA and FENa with undetectable DOPA levels in the urine in EHT. In addition, under the basal condition, UDA correlated positively with p-DOPA or the product of p-DOPA x Ccr, which might reflect the DOPA delivery at the renal proximal tubule. No significant difference was found in p-DOPA and the product of p-DOPA x Ccr among NT, NRH and LRH. However, the ratio of UDA/(p-DOPA x Ccr), which may indicate the conversion from DOPA to DA in the kidneys, was lower in EHT, especially in LRH, than that in NT. These results suggest that a reduced renal conversion from DOPA to DA may contribute to the attenuated natriuresis as well as renal dopaminergic activity in LRH.

Studies were conducted to evaluate the role of water-sodium balance and renal dopaminergic activity in the hypertensive mechanisms of overweight patients with essential hypertension (EHT). The body mass index (BMI) was correlated positively with mean arterial pressure, plasma volume, extracellular fluid volume, or total exchangeable sodium and negatively with plasma noradrenaline concentration or plasma renin activity in patients with EHT. Fractional excretion of sodium (FENa) was significantly lower in overweight patients than in normal weight patients with EHT. Hypotensive effect of sodium restriction or the natriuretic response to infused dopamine was more remarkable in overweight patients with EHT than in normal weight patients with EHT. Urinary excretion of free dopamine (UDA) was correlated positively with simultaneously measured urinary excretion of sodium or FENa and negatively with the natriuretic response to dopamine infusion. In addition, UDA was positively correlated with the BMI in normal weight patients with EHT, whereas the relation between the UDA and the BMI was significantly negative in overweight patients with EHT. These findings suggest that the expansion of body fluid volume and sodium might result from the blunted natriuretic ability due to an attenuation of the renal dopaminergic activity in overweight patients with EHT. The expansion of body fluid volume and sodium may play an important role in the hypertensive mechanisms of overweight patients with EHT.

To evaluate the role of the renal dopaminergic system on renal water-sodium metabolism patients with essential hypertension (EHT), urinary excretion of dopamine, urinary excretion of sodium (UNaV) and fractional excretion of sodium (FENa) were all investigated before and after the administration of dopamine (3 micrograms/kg/min, intravenous infusion for 60 minutes), dopamine antagonist, metoclopramide (8 mg/m2 BSA, intravenous injection) or mild sodium loading in both normotensive subjects and benign EHT. In the basal values, no significant difference in urinary excretion of free (u-fDA), conjugated (u-cDA) or total dopamine (u-tDA) was found between normotensives and hypertensives. However, low renin EHT showed a pronounced reduction in u-fDA compared with normotensis subject and (NT) normal renin EHT. In this study, a significant reduction of u-cDA and of u-tDA was also found in those patients with low renin essential hypertension. In the normotensive and essential hypertensive groups UNaV or FENa showed a positive correlation with u-fDA (measured simultaneously), but not with u-tDA or u-cDA. The regression line between u-fDA and UNaV or FENa in EHT was shifted towards a lower u-fDA level than in NT. UNaV and FENa were increased by dopamine infusion and were decreased by metoclopramide injection in both NT and EHT. Changes of UNaV and FENa following dopamine or metoclopramide, showed a negative correlation with u-fDA measured immediately before the administration of these drugs. The enhanced natriuretic response to infused dopamine and the attenuated antinatriuretic response to injected metoclopramide were significant in low renin EHT, when compared with NT or normal renin EHT patients.(ABSTRACT TRUNCATED AT 250 WORDS)