Urinary dopamine, noradrenaline and adrenaline in type 2 diabetic patients with and without nephropathy

We measured the urinary excretions of dopamine, noradrenaline and adrenaline, their conjugated metabolites, urinary excretion of sodium and creatinine clearance simultaneously in 21 patients with Type 2 (non-insulin-dependent) diabetes and 6 normal subjects. The mean (+/- SEM) value for urinary excretion of dopamine (52.4 +/- 8.8 micrograms/day) in diabetic patients with nephropathy (Group C, n = 12) was significantly lower (P less than 0.01) than in the normal subjects (Group A, 179.7 +/- 15.5 micrograms/day) and in diabetic patients without nephropathy (Group B, n = 9, 131.5 +/- 16.5 micrograms/day). The mean values for the urinary excretions of noradrenaline and adrenaline were also significantly lower (P less than 0.01) in Group C than in Groups A and B. In addition, the mean urinary excretion of conjugated metabolite of dopamine in Group C was significantly lower (P less than 0.05) than in Group A. There was a trend toward the observation that the mean 24-h urinary excretion of sodium in Group C (121.6 less than 12.9 mEq) was lower as compared with that in Group A (140.8 +/- 8.9 mEq) or B (150.7 +/- 17.9 mEq). A multiple regression analysis revealed that the 24-h urinary excretion of dopamine correlated significantly with creatinine clearance, systolic (P less than 0.01) and diastolic (P less than 0.05) blood pressures. The results indicate that synthesis or secretion of renal dopamine might decrease with a progression of diabetic nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relations between the renin-angiotensin-aldosterone system and urinary elimination of sodium: study of healthy subjects in clinostatism and on a sodium-free diet

In 94 normotensive subjects and free sodium diet, the relationship between SPRA and the 2-hour urinary sodium excretion was significantly better fitted by an hyperbolic function (p less than 0,001); r = 0,53) than a linear one (p less than 0,001; r = -0,31) between SPRA and the 24-hour urinary sodium excretion. (SPRA = Supine Plasma Renin Activity).     

Plasma atrial natriuretic peptide in conscious rats with reduced renal mass

The effect of salt intake and reduction of renal mass (RRM) on plasma immunoreactive atrial natriuretic peptide (iANP) levels in conscious rats was studied. Rats were divided into RRM and sham-operated groups, and then further subdivided into groups infused with 1 or 6 mEq of sodium per day. Plasma urea nitrogen increased in the groups with RRM. Plasma sodium, sodium balance, and heart rate did not differ between the sham and RRM groups. Rats with RRM maintained on 1 mEq of sodium per day did not have an elevation of water intake, arterial pressure, or plasma iANP. Rats with RRM maintained on 6 mEq of sodium per day had significantly (P less than 0.05) elevated water intake, arterial pressure, and plasma iANP. Arterial pressure and plasma iANP were correlated (r = 0.800) for rats with RRM on either 1 or 6 mEq of sodium per day. Increased plasma iANP in the RRM group on 6 mEq per day was not caused by either RRM or high sodium alone; it was an effect of RRM plus high salt intake. The increase in plasma iANP in the RRM group may be caused by the increase in arterial pressure, possibly due to an increase in extracellular fluid volume. ANP may not be responsible for the sustained increase in fractional sodium excretion observed in RRM.     

Response of plasma aldosterone to orthostatism during follicular and luteal phases of the normal menstrual cycle

The responses of plasma aldosterone (A) and plasma renin activity (PRA) to orthostatism have been evaluated in 47 women during the follicular and/or luteal phase of the menstrual cycle. Three postmenopausal women and 51 men were also studied for control. Fourteen cycling women and 11 men were studied on a low sodium diet (20 mEq/day) while the rest of the subjects were on normal sodium intake. In addition, 18 women (including those postmenopausal) and 17 men were studied after intravenous administration of 20 mg frusemide. The response of A to orthostatism in women during luteal phase on normal sodium diet with or without frusemide was much greater than in men or women during follicular phase (p less than 0.01) or menopuase (p less than 0.05). However, no differences between groups could be observed in A response while on a low sodium diet. PRA response was similar during follicular of luteal phase fo the cycle as well as in men either on low or normal sodium intake with or without frusemide.     

Endogenous digoxin-like factor: serum concentration and interrelations with the electrolyte picture in normal subjects

Endogenous Digitalis-Like Factor (DLF) is a putative hypothalamic Na+,K+-ATPase inhibitor that mediates natriuresis in response to intravascular volume expansion or sodium loading. The precise structure of this substance remains unknown; however, it cross-reacts with antibody to digoxin. Using a radioimmunoassay, we measured DLF concentrations in 26 normal subjects: mean value of this factor was 0.512 ng digoxin-equivalents/ml +/- 0.038 SEM; DLF correlated significantly with serum sodium levels (r = 0.59 - p less than 0.01) and daily urinary sodium excretion (r = 0.48 - p less than 0.05). Our results confirm that endogenous digitalis-like factor has a physiological role as regulator of natriuresis, in response to plasma sodium concentrations.     

A possible contribution of endogenous atrial natriuretic peptide to proteinuria in patients with chronic renal failure.

Plasma levels of immunoreactive atrial natriuretic peptide (IR-ANP) were measured with a specific radioimmunoassay in 19 undialysed patients with chronic renal failure. At the beginning, an extremely high level of plasma hANP (50 fmol/ml) seen in a patient was rejected with Smirnov's test and was excluded from further statistics. The plasma IR-ANP levels in these patients were significantly higher than those of 19 normal subjects matched with age and sex (10.9 +/- 1.6 vs 5.3 +/- 0.6 fmol/ml, mean +/- SEM, p less than 0.01), and positively correlated with mean blood pressure (r = 0.44, p less than 0.05) and the cardiothoracic ratio (r = 0.65, p less than 0.01), but did not correlate with creatinine clearance (r = -0.38, n.s.). Further, a significant correlation was observed between plasma IR-ANP and urinary protein output (r = 0.47, p less than 0.05). On the other hand, urinary protein output did not correlate significantly with variables such as mean blood pressure, the cardiothoracic ratio or creatinine clearance. Since it has been suggested that ANP enhances glomerular capillary permeability, increased ANP responding to volume overload in those patients may play an important role in increasing urinary protein excretion.     

Serum aldosterone and protein-binding variables in Yanomama Indians: a no-salt culture as compared to partially acculturated Guaymi Indians

Yanomama Indians from the jungles of southern Venezuela and northern Brazil excreted 1 +/- 1.5 mEq of Na and 203 +/- 109 mEq of K and had low blood pressure (BP), 102/62 mm Hg). In comparison, Guaymi Indians of Panama excreted 103 +/- 50 mEq of Na and 118 +/- 52 mEq of K and had significantly higher BP (114/75 mm Hg, p less than 0.001). Elucidating the renin-aldosterone axis, total upright serum aldosterone in 34 Yanomama was high (85.6 +/- 78 ng/100 ml). The binding capacities of thermolabile (ABG) and thermostable (ABG-Ts) serum globulins for aldosterone were elevated at 23.8 +/- 6 and 14.9 +/- 2.6%, respectively; consequently, total ABG- plus ABG-Ts- bound aldosterone was as high as 38.6 +/- 6.3%. Plasma renin activity (PRA 10.3 +/- 2.4 ng/ml/h) and urinary aldosterone 18-glucuronide (70.3 +/- 30 micrograms/24 h) in 17 Yanomama were also very high. In contrast, total serum corticosteroids and corticosteroid-binding globulin (CBG) binding capacity were normal, suggesting normal ACTH activity. PRA correlated positively with total (r = 0.47, p less than 0.05) and free (r = 0.47, p less than 0.05) serum aldosterone, which in turn showed a negative trend with Na (r = 0.33, NS) excretion. The effect of high dietary K appeared less important to aldosterone stimulation and PRA suppression. ABG-bound aldosterone (r = 0.43, p less than 0.01) as well as ABG-Ts (r = 0.56, p less than 0.05) were negatively correlated with diastolic but not systolic BP. The total ABG- and ABG-Ts-bound fraction correlated with diastolic BP (r = 0.43, p less than 0.05) in contrast to the free fraction (r = 0.08, NS) or total aldosterone (r = -0.09). Apparently, only bound serum aldosterone is important for the maintenance of diastolic BP. High serum aldosterone, with elevated excretion, indicates an increased secretion rate; increased serum protein binding suggests an increased tissular activity and alterations in aldosterone metabolism. In Guaymi Indians both total plasma aldosterone (14.5 +/- 65 ng/100 ml) and urinary aldosterone (8.1 +/- 4.8 micrograms/creatinine excretion) were normal. ABG-binding capacity for aldosterone was moderately elevated (17.8 +/- 4.8) and of ABG-Ts normal (10.2 +/- 1.2) suggesting a nearly normal aldosterone metabolism and regulation. The BP of Guaymi was significantly higher than that of the Yanomama.     

Role of atrial natriuretic peptide and urinary cGMP in the natriuretic and diuretic response to central hypervolemia in normal human subjects

The response of plasma atrial natriuretic peptide (ANP) and urinary cGMP excretion to central hypervolemia induced by water immersion was assessed twice in five healthy male subjects, once while immersed in water to the neck for 3 h and again on a control day. Plasma ANP and urinary cGMP were measured by radioimmunoassay. Compared with the control day, overall change in plasma ANP on the immersion day was significant (p less than 0.05). In response to water immersion, plasma ANP increased from a base-line level of 13.2 +/- 3.1 (mean +/- SEM) to 24.2 +/- 5.5 pg/mL by 0.5 h of immersion and was sustained at that level throughout the immersion period. Plasma ANP returned to the base-line level at 1 h postimmersion. Urinary cGMP excretion increased significantly by 1 h of immersion and was sustained at that level throughout water immersion and 1 h postimmersion (p less than 0.05). During water immersion urine flow, urinary sodium and potassium excretion, free water clearance, and osmolar clearance increased while plasma renin activity, serum aldosterone, and blood pressure fell; all changes were significant (p less than 0.05). Creatinine clearance and hematocrit did not show any significant changes. These data suggest that an increase in plasma ANP may contribute to the natriuretic and diuretic response to central hypervolemia, and that the measurement of urinary cGMP may be a valuable marker of ANP biological responsiveness.     

Evidence for a dual action of converting enzyme inhibitor on blood pressure in normal man

We studied the effect of a converting enzyme inhibitor (CEI), Captopril SQ 14,225 50 mg p.o. in eight supine normal subjects under a high sodium (150 mEq/d) and low sodium (25 mEq/d) diet. On high sodium, plasma renin (PRA) and aldosterone were basal and Saralasin did not lower mean blood pressure. However, CEI induced an 11.4 +/- 3.2 mm fall in blood pressure (p less than 0.02) and either indomethacin 50 mg or ibuprofen 800 mg (PI), when given simultaneously on another day abolished the blood pressure response (2.5 +/- 0.9 mm Hg, p greater than 0.5). In contrast, on a low salt diet where renin was increased, CEI induced a drop in blood pressure which was not significantly altered by PI (12.8 +/- 1.1 vs. 10.0 +/- 3.1 mm Hg, p greater than 0.5). CEI increased plasma renin on both diets (1.7 +/- 0.5 to 3.5 +/- 0.8 and 2.8 +/- 0.6 to 12.5 +/- 3.1 ng/ml/hr respectively both p less than 0.05). Aldosterone did not change (high Na+) or fell (low Na+). Inhibition of Prostaglandin synthesis did not significantly block the renin rise from CEI suggesting that the direct angiotensin II negative feedback is relatively independent of acute prostaglandin release. Our studies suggest that CEI has a dual hypotensive action. In a low renin state, the hypotensive action appears to be mediated through vascular prostaglandins.     

Plasma concentration of antidiuretic hormone in patients with chronic renal insufficiency on maintenance dialysis.

Radioimmunoassay of plasma arginine-vasopressin (AVP) in regularly dialyzed patients with chronic renal insufficiency revealed a parallel increase of AVP and plasma osmolality (POsm) before dialysis (4.16 +/- 0.36 pg/ml and 312.6 +/- 1.80 mOsm/1) and their parallel declin to the normal range (1.93 +/- 0.27 pg/ml and 292.0 +/- 1.27 mOsm/1) during dialysis. Plasma AVP correlated with POsm before and after dialysis (r = 0.611 and 0.453, p less than 0.01 and less than 0.05 respectively). The increase of AVP before dialysis was lower than would correspond to the rise of POsm and lower than that recorded in healthy subjects during dehydration. Statistical correlation between plasma AVP and indicators of body fluid volume changes between or during dialysis were not proved. We found statistical correlation between the mean blood pressure and AVP before dialysis (r = 0.468, p less than 0.05). These findings suggest that in chronic renal insufficiency changes of POsm remain primary regulating factor of AVP secretion. The expansion of extracellular fluid volume has probably only a modifying effect. It remains to be elucidated whether the revealed statistical relationship between the mean blood pressure and AVP before dialysis plays also a pathogenetic role in the development of hypertension in chronic renal insufficiency.     

Effects of ACTH on plasma levels of adrenal steroids in essential hypertension.

Plasma concentrations of progesterone (P), deoxycorticosterone (DOC), 17-hydroxyprogesterone (17-OH P), corticosterone (B), deoxycortisol (S), cortisol (F) and aldosterone (A) in 8 control subjects (mean age: 40.5 years) and 10 patients with essential hypertension (EH) (mean age: 48.5 years) were determined before, 4 and 8 hours after an infusion of ACTH at a rate of 25 units per 8 hours. Secretion rates (SR) of 18-hydroxy-11-deoxycorticosterone (18-OH DOC) were measured 24 hours before and again on the day of ACTH infusion. All subjects were studied on the fourth day of a diet containing 135 mEq of sodium and 90 mEq of potassium. There was no statistically significant difference between 8 control subjects and 10 patients with EH in the 7 plasma steroid levels and the SR of 18-OH DOC before ACTH infusion. The mean plasma P response to ACTH was slightly lower in controls than in patients with EH, while that of 17-OH P (in male subjects) was slightly higher. The mean plasma B response was significantly lower after 4 hours of ACTH infusion (p less than 0.01), while that of DOC was significantly higher after 8 hours of ACTH infusion (p less than 0.05) in patients with EH. The mean plasma S rose significantly more in patients with EH (p less than 0.025) at 4 and 8 hours after ACTH infusion. The mean plasma F response to ACTH infusion was slightly lower in patients with EH than in controls. The mean response of 18-OH DOC SR to ACTH infusion was slightly higher in patients with EH than in controls. The mean plasma A response was significantly higher in patients with EH than in controls 4 (p less than 0.05) and 8 hour (p less than 0.001) after an ACTH infusion. These results could be explained in part by abnormalities in the 17- and 11-hydroxylase systems, and that the abnormality in 11-hydroxylation was more pronounced than that in the 17-position. Furthermore, we suspect that the sensitivity of adrenal aldosterone to ACTH might be increased or another accelerated pathway to aldosterone biosynthesis might exist in patients with EH.     

Possible role of renal prostaglandin E2 in natriuresis associated with supraventricular tachycardia

We investigated the possible role of renal prostaglandin (PG) E2 in natriuresis associated with supraventricular tachycardia (SVT). In five female patients with paroxysmal tachycardia, SVT was artificially induced and then stopped 60 min later. Before, during, and after SVT, plasma levels of arginine vasopressin and atrial natriuretic peptide (ANP) and the urinary excretion of sodium and PGE2 were measured. Polyuria was observed during SVT. However, natriuresis did not occur until immediately after the termination of SVT. During SVT, the plasma levels of arginine vasopressin tended to decrease. When SVT was terminated, the vasopressin levels increased significantly (p less than 0.01). Urinary excretion of PGE2 tended to decrease during SVT and then increased significantly (p less than 0.01) after SVT ended. Urinary excretion of sodium was correlated (r = 0.699, p less than 0.001) with the urinary excretion of PGE2. Plasma ANP increased during SVT, but there was no correlation with urinary sodium excretion. These results suggest that renal PGE2, the biosynthesis of which may be stimulated by a increase in plasma vasopressin, is an important factor contributing to the natriuresis observed after the end of SVT.     

Salt intake and depletion increase circulating levels of endogenous ouabain in normal men

High-salt diets elevate circulating Na+ pump inhibitors, vascular resistance, and blood pressure. Ouabain induces a form of hypertension mediated via the alpha2-Na+ pump isoform and the calcium influx mode of the vascular sodium calcium exchanger (NCX). Whereas elevated levels of an endogenous ouabain (EO) and NCX have been implicated in salt-sensitive hypertension, acute changes in sodium balance do not affect plasma EO. This study investigated the impact of longer-term alterations in sodium balance on the circulating levels and renal clearance of EO in normal humans. Thirteen normal men consumed a normal diet, high-salt diet, and hydrochlorothiazide (HCTZ), each for 5-day periods to alter sodium balance. EO and other humoral and urinary variables were determined daily. On a normal diet, urinary sodium excretion (140 +/- 16 meq/day), plasma EO (0.43 +/- 0.08 nmol/l) and urinary EO excretion (1.04 +/- 0.13 nmol/day) were at steady state. On the 3rd day of a high-salt diet, urine sodium excretion (315 +/- 28 meq/day), plasma EO (5.8 +/- 2.2 nmol/l), and the urinary EO excretion (1.69 +/- 0.27 nmol/day) were significantly increased, while plasma renin activity and aldosterone levels were suppressed. The salt-evoked increase in plasma EO was greater in older individuals, in subjects whose baseline circulating EO was higher, and in those with low renal clearance. During HCTZ, body weight decreased and plasma renin activity, aldosterone, and EO (1.71 +/- 0.77 nmol/l) rose, while urinary EO excretion remained within the normal range (1.44 +/- 0.31 nmol/day). Blood pressure fell in one subject during HCTZ. HPLC of the plasma extracts showed one primary peak of EO immunoreactivity with a retention time equivalent to ouabain. High-salt diets and HCTZ raise plasma EO by stimulating EO secretion, and a J-shaped curve relates sodium balance and EO in healthy men. Under normal dietary conditions, approximately 98% of the filtered load of EO is reabsorbed by the kidney, and differences in the circulating levels of EO are strongly influenced by secretion and urinary excretion of EO. The dramatic impact of high-salt diets on plasma EO is consistent with its proposed role as a humoral vasoconstrictor that links salt intake with vascular function in hypertension.     

Effects of dietary copper on human autonomic cardiovascular function

Heart rate and blood pressure responses during supine rest, orthostasis, and sustained handgrip exercise at 30% maximal voluntary contraction were determined in eight healthy women aged 18-36 years who consumed diets varying in copper and ascorbic acid content. Copper retention and plasma copper concentration were not affected by diet. Enzymatic, but not immunoreactive, ceruloplasmin was lower (p less than 0.05) after the low copper and high ascorbic acid diet periods. Diet had no effect on resting supine heart rates, orthostatic responses in heart rate and blood pressure, or standing resting blood pressure. Systolic and diastolic blood pressures were increased significantly (p less than 0.05) during the handgrip test at the end of the low copper and ascorbic acid supplementation periods. Also, the ratio of enzymatic to immunoreactive ceruloplasmin decreased significantly during these dietary treatments. The mean arterial blood pressure at the end of the handgrip test was negatively (p less than 0.0004) correlated with the ceruloplasmin ratios. These findings indicate a functional alteration in human blood pressure regulation during mild copper depletion.     

心钠素对卒中易感型自发性高血压大鼠血浆和脑组织加压素的影响

为研究心钠素(ANF)和精氨酸加压素(AVP)的相互作用在原发性高血压发病中的意义,对卒中易感型自发性高血压大鼠(SHRsp)和对照大鼠(WKY)侧脑室(icv)或静脉(iv)注射人ANF-(99-126)观察其对血浆、下丘脑和垂体AVP含量以及平均动脉压(MAP)和尿量(UV)、尿钠(U_(Na)V)排泌的影响。静脉注射ANF后10min,SHRsp和WKY大鼠的MAP分别下降9.4％和12.2％(P<0.05),UV分别增加9和20倍(P<0.01),U_(Na)V增加16和29倍(P<0.01)。侧脑室注射ANF对两种大鼠的MAP、UV和U_(Na)V排泌均无明显作用。静脉或侧脑室注射ANF均使两种大鼠的血浆AVP水平明显下降,其中SHRsp的血浆AVP浓度下降程度(iv,-58％;icv,-31％)弱于WKY大鼠(iv,-80％;icv,-65％),下丘脑AVP含量在两种大鼠中都明显增加,而垂体AVP含量无明显变化。 结果表明,人ANF-(99-126)有明显的抑制AVP释放和降压、利尿、利纳作用,而SHRsp对这些作用的敏感性都降低,提示SHRsp对ABF的反应减弱可能在自发性高血压大鼠的发病中具有一定的意义。     

Effects of a nonperssor analogue of vasopressin on plasma renin activity and salt and water excretion in water-loaded,anesthetized dogs

The object of this study was to determine the importance of vasoconstrictor activity in the suppression of renin secretion by vasopressin. Arginine vasopressin (AVP) (0.05 and 0.1 ng/kg/min) and a nonpressor analogue of vasopressin, 1-deamino-[4-threonine, 8-D-arginine]-vasopressin (dTDAVP) (0.01 and 0.05 ng/kg/min), were infused intravenously in anesthetized hypophysectomized dogs. Neither dTDAVP nor AVP influenced arterial pressure or heart rate but both suppressed plasma renin activity. Infusion of dTDAVP at 0.01 and 0.05 ng/kg/min suppressed plasma renin activity to 86±4% (p<0.05) and 63±6% (p<0.01) of the control values respectively. Infusion of AVP at 0.05 and 0.1 ng/kg/min suppressed plasma renin activity to 60±8% (p<0.01) and 59±12% (p<0.05) of the central values respectively. dTDAVP and AVP both produced significant increases in sodium excretion. These data demonstrate that vasoconstrictor activity is not required for the effects of vasopressin on renin secretion and sodium excretion.     

Moderate sodium restriction with angiotensin converting enzyme inhibitor in essential hypertension: a double blind study.

Fifteen unselected patients who had essential hypertension and whose average supine blood pressure when they were not receiving any treatment and their usual sodium intake was 162/107 mm Hg were treated with captopril 50 mg twice daily. After one month''s treatment their supine blood pressure had decreased to 149/94 mm Hg. They were then instructed to reduce their sodium intake to about 80 mmol(mEq)/day. After two weeks of moderate sodium restriction they were entered into a double blind randomised crossover study comparing the effect of 10 Slow Sodium tablets (100 mmol sodium chloride) with matching placebo tablets while continuing to take captopril and restrict sodium in their diet. After one month of taking placebo their mean supine blood pressure was 137/88 mm Hg with a urinary sodium excretion of 83 mmol/24 h, while after one month of taking Slow Sodium tablets their mean supine blood pressure was 150/97 mm Hg (p less than 0.001) with a sodium excretion of 183 mmol/24 h. The mean supine blood pressure during moderate sodium restriction therefore decreased by 9% and correlated significantly with the reduction in urinary sodium excretion. These results suggest that the combination of treatment with a moderate but practical reduction in sodium intake and an angiotensin converting enzyme inhibitor is effective in decreasing the blood pressure in patients with essential hypertension. This combined approach overcomes some of the objections that have been made to salt restriction alone and to converting enzyme inhibitors alone.     

Vasoactive factors in decompensated cirrhosis. Effect of acute plasma expansion

Plasma volume expansion was performed in 16 cirrhotic patients with ascites, 8 with avid sodium retention (sodium retainers) and 8 with normal sodium balance (sodium excretors). No natriuretic response was observed in sodium retainers (daily UNa = 7.1 +/- 1.5 mEq before expansion and 20.8 +/- 7.8 after expansion; p = not significant). After expansion plasma renin activity and plasma aldosterone showed a fall in both groups, whereas urinary kallikrein excretion decreased significantly in sodium retainers (27.1 +/- 9.7 before expansion and 7.8 +/- 6.4 after expansion; p less than 0.05). Baseline PGE were higher than normal in sodium retainers (997.0 +/- 134.3; p less than 0.02 vs. controls) and increased after expansion. Plasma octopamine was always within normal range. These results suggest that: a) reduction of effective plasma volume is not the main factor involved in sodium retention; b) the renin-angiotensin-aldosterone system has only a permissive role; c) prostaglandin system is activated and could have a protective role in maintaining renal function in cirrhotic patients.     

Angiotensin II mediates hyperadrenergic activity evoked by sodium restriction in essential hypertension

We examined the possible involvement of angiotensin II in the modulation of circulating norepinephrine produced by acute sodium restriction in essential hypertensive patients (n = 18). Sodium restriction potentiated plasma level of norepinephrine in parallel with an increased plasma renin activity (r = 0.81, F = 31.2, p less than 0.05 given by the percent changes). An intravenous infusion of sarcosine-1, isoleucine-8 angiotensin II produced a significant fall in mean arterial pressure (-6 +/- 2 mmHg, p less than 0.05) in patients on sodium restriction but not before sodium restriction, while the infusion of the antagonist produced a greater decrease (p less than 0.05) in plasma norepinephrine with sodium restriction (-158 +/- 23 pg/ml, p less than 0.05) when compared to that obtained before sodium restriction (-91 +/- 11 pg/ml, p less than 0.05). A single oral administration of an angiotensin I converting enzyme inhibitor, captopril caused a greater fall (p less than 0.01) in mean arterial pressure after sodium restriction (-32 +/- 3 mmHg, p less than 0.05) compared to that given before (-21 +/- 3 mmHg, p less than 0.05). However, sodium restriction did not affect the magnitude of reflex increase in plasma norepinephrine to hypotension evoked by captopril (from +88 +/- 16 pg/ml to +87 +/- 17 pg/ml; p greater than 0.05). It can be interpreted that acute sodium depletion results in a substantial contribution of angiotensin II to the expression of hyperadrenergic activity.     

Relationship between renal and cardiovascular changes in a murine model of glucose intolerance

Nutrition is an important variable which may affect the risk for renal disease. We previously showed that a high fructose diet in mice produced hypertension and sympathetic activation [8]. The purpose of this study was to determine if a fructose diet altered renal function. A high fructose diet for 12 weeks impaired glucose tolerance, but caused no change in body weight, blood glucose or plasma insulin. Impairment in renal function was documented by the almost two fold increase in urinary protein excretion (Control: 6.6+/-0.6 vs. Fructose: 15.0+/-0.7 mmol protein/mmol creatinine; p<0.05) which was also accompanied by increases in urinary volume. The diet produced little change in renal histology, kidney weight or kidney weight/body weight ratio. Urinary excretion of angiotensin II/creatinine (Control: 78.9+/-16.6 vs. Fructose: 80.5+/-14.2 pg/mmol) and renal angiotensin converting enzyme activity (Control: 9.2+/-1.6 vs. Fructose: 7.6+/-1.0 ACE units) were not different between groups. There was a positive correlation between mean arterial pressure (r=0.7, p=0.01), blood pressure variability (BPV) (r=0.7, p=0.02), low frequency BPV component (r=0.677, p=0.03) and urinary protein excretion. Results show that consumption of a high fructose diet in mice had deleterious effects on renal function, which were correlated with cardiovascular changes.