Decrease In Renal Plasma Flow Research Articles

Role of nitric oxide in long-term angiotensin II-induced renal vasoconstriction.

In vitro studies have indicated that nitric oxide may play an important role in modulating the renal vascular actions of angiotensin II (Ang II). However, the physiological importance of this interaction in the long-term regulation of renal hemodynamics is unknown. Therefore, the goal of this study was to determine if long-term Ang II-induced renal vasoconstriction was potentiated by nitric oxide synthesis inhibition. The intrarenal effects of Ang II were examined in eight unilaterally nephrectomized, conscious dogs before and after systemic inhibition of nitric oxide synthesis. Ang II infusion into the renal artery at 0.5 ng/kg per minute resulted in decreases in renal plasma flow of 15% and 9% after 3 and 5 days, respectively. During this time, glomerular filtration rate decreased 12% after 3 days of angiotensin but was not significantly changed after 5 days. After 4 days of recovery from Ang II, nitric oxide synthesis was inhibited with intravenous NG-nitro-L-arginine-methyl ester (L-NAME) at 10 micrograms/kg per minute for 5 days, and this caused a significant decrease in renal plasma flow but no change in glomerular filtration rate. Infusion of Ang II into L-NAME-pretreated dogs for an additional 5 days further decreased renal plasma flow and glomerular filtration 14% and 11%, respectively. However, the effects of Ang II and L-NAME on renal plasma flow were only additive on days 3 and 5 of this period, and the effects on glomerular filtration were additive on day 3 but were potentiated on day 5.(ABSTRACT TRUNCATED AT 250 WORDS)

Preserving the Autoregulation of Renal Hemodynamics

Renal hemodynamics in essential hypertensives is characterized by an increase in renal vascular resistance (RVR) and a decrease in renal plasma flow (RPF), while glomerular filtration rate (GFR) is either normal or slightly decreased. Filtration fraction (FF) is increased, indicating that vasoconstriction predominantly affects postglomerular arteries. This increase in FF, called hyperfiltration, can be regarded as a successful maintenance of a normal glomerular filtration but can be deleterious for long-term renal function by favoring the development of glomerulosclerosis. Administration of some beta-blockers (especially propranolol) to hypertensive patients still reduces RPF and GFR, and increases FF. Conversely, in short-term studies, tertatolol has been shown to reduce RVR and increase RPF, without altering FF in hypertensive patients. These effects correspond to a normalization of the renal hemodynamic profile. Their practical interest is however strongly dependent on their persistence in long-term treatment. The beneficial effects of tertatolol were confirmed in 3 long-term studies, lasting for one year. These three studies yielded remarkably similar results: there was a modest overall decrease in serum creatinine, and a more pronounced drop in patients whose pretreatment renal function was altered. These data suggest that tertatolol may preserve the long-term autoregulation of renal hemodynamics. The possibility is raised that in patients with minimal renal dysfunction, tertatolol may also slow down the progression of renal failure.

Renal response to indomethacin in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

The impact of nonsteroidal anti-inflammatory drugs (NSAIDs) on renal function has not been evaluated in patients with congestive heart failure. Therefore, the renal effects of indomethacin were examined in patients with chronic heart failure, and the relation between the changes in glomerular filtration rate and renal plasma flow after indomethacin administration was assessed. Twenty-five patients with congestive heart failure and an ejection fraction less than 40% were evaluated. At baseline, renal plasma flow and glomerular filtration rate were measured, using disappearance from the serum of intravenously injected 131I-orthodihippurate and urinary accumulation of intravenously injected technetium-99m diethylenetriamine pentaacetic acid, respectively. After 3 days, 75 mg of sustained release indomethacin were administered, and repeat renal function tests were performed. Mean glomerular filtration rate decreased from 40 +/- 21 to 32 +/- 16 ml/min/1.73 m2 (p less than 0.05), and mean renal plasma flow decreased from 242 +/- 122 to 222 +/- 110 ml/min/1.73 m2 (p less than 0.05). There was no correlation between the changes in glomerular filtration rate and renal plasma flow after indomethacin administration. It is concluded that 1 dose of an NSAID may cause marked and clinically important alterations in renal function in patients with heart failure. However, the decrease in glomerular filtration rate does not merely reflect a decrease in renal plasma flow, but probably the effects of NSAIDs on the intraglomerular actions of prostaglandins.

Glomerular hemodynamics and hormonal evaluation during starvation in rats.

The effects of total food deprivation on renal function were evaluated in normal Munich-Wistar rats submitted to starvation (S) periods of two to eight days (Groups S2 to S8). A prompt and sustained decrease in renal plasma flow (RPF) and an increase in total renal vascular resistance (TRVR) were observed after the second day, together with a gradual decrease in glomerular filtration rate (GFR) until the fourth day (40% in the S4 group, P less than 0.05). After this period, a spontaneous and progressive increase in GFR occurred in spite of continuing low RPF and high TRVR. Glomerular hemodynamics were evaluated in additional animals from groups S4 and S7. As observed for whole kidney GFR, mean single nephron (SN) GFR was reduced in group S4, but not in group S7. The decline in SNGFR in S4 was the result of a decline (approximately 40%) in glomerular plasma flow rate (QA) and glomerular capillary hydraulic pressure (PGC), due to a predominant increase (approximately 60%) in afferent arteriolar resistance. In S7, SNGFR and its determinants did not differ from the control. Angiotensin II (Ang II), prostaglandin (but not thromboxane A2, TxA2) inhibition blunted the alterations in whole kidney function observed in S4. Conversely in S7, the inhibition of vasoconstrictor agents (Ang II and TxA2) did not normalize GFR, suggesting that the intrarenal vasoconstriction could be an important factor to maintain GFR after a prolonged period of starvation.(ABSTRACT TRUNCATED AT 250 WORDS)

Control of renal hemodynamics during intrarenal and systemic blockade of nitric oxide synthesis in conscious dogs.

Systemic blockade of nitric oxide (NO) synthesis results in marked increases in the renal vascular resistance (RVR) and decreases in the glomerular filtration rate (GFR) and renal plasma flow (RPF). The renal hemodynamic effect of systemic NO blockade is most likely due to an integration of direct and indirect renal actions. The quantitative importance of local intrarenal blockade of NO synthesis on renal hemodynamics has not been fully elucidated. Therefore, the purpose of this study was to compare the renal hemodynamic effects of intrarenal vs. systemic NO synthesis blockade on renal hemodynamics. Nitro-L-arginine methyl ester (L-NAME) was infused intrarenally at a rate of 3 micrograms/kg/min for 180 min in conscious chronically instrumented dogs (n = 7). Intrarenal infusion of L-NAME for 180 min resulted in a 12% decrease in RPF, 14% increase in RVR, and no effect on mean arterial pressure (MAP) or GFR. In contrast, infusion of L-NAME intravenously at a rate of 10 micrograms/kg/min for 180 min increased the RVR by 124% and decreased the RPF by 55% and GFR by 45%. The MAP and heart rate both increased in response to intravenous administration of L-NAME. The results of this study suggest that the renal hemodynamic effects of systemic administration of L-NAME may, in large part, be secondary to extrarenal effects of NO synthesis blockade, possibly via activation of the sympathetic nervous system.

Renal cortical intermediary metabolism in the recovery phase of postischemic acute renal failure in the dog.

Renal metabolism has been studied in eight dogs before and 48 hr after a 60-min period of renal ischemia induced by clamping the left renal artery with the simultaneous removal of the right kidney, and in 12 sham-operated animals. The study involved the measurement of renal uptake and production of lactate, glutamine, glutamate, alanine, ammonium, and oxygen, and the measurement of the tissue concentrations of ATP, glutamine, lactate, alpha-ketoglutarate, aspartate, and alanine in the renal cortex. Two days after a temporary renal ischemia, the remaining kidney showed a 22% decrease in glomerular filtration rate (GFR) and a 25% decrease in renal plasma flow. Fractional sodium and potassium excretions were similar to those of control dogs. Renal production or extraction of glutamine, glutamate, alanine, ammonium, and oxygen (all expressed by 100 ml of GFR) was not significantly different in basal conditions or 2 days after ischemia, but lactate extraction was reduced in postischemic kidneys (-101 +/- 29 vs -204 +/- 38 mumol/100 ml GFR in control dogs). The cortical concentrations of glutamine and glutamate were lower in postischemic than in control kidneys. No differences were found in cortical concentration of alpha-ketoglutarate, aspartate, lactate, pyruvate, or ATP, but total nucleotides and inorganic phosphate were decreased in postischemic kidneys. It is concluded that in the recovery phase of the ischemia, a decreased lactate uptake is the main metabolic change, and total ATP production is adapted to the decrease of GFR and sodium reabsorption.

Effect of lysophosphatidylcholine on renal hemodynamics and excretory function in anesthetized rats

The effect of myristoyl-lysophosphatidylcholine (myristoyl-LPC) on renal hemodynamics, electrolyte and water excretion was examined over a 90 min period in sodium pentobarbital anesthetized male Sprague Dawley rats. Intravenous infusion of myristoyl-LPC at 13 ± 3 pmol/min resulted in a small fall in systemic blood pressure, a 13% decrease in renal plasma flow without significantly altering glomerular filtration rate and produced a slightly greater excretion of sodium and water than vehicle controls. These results suggest that short term myristoyl-LPC administration can significantly alter renal function producing a weak natriuresis and diuresis which is not dependent on systemic blood pressure and renal hemodynamic changes.

Effect of somatostatin on kidney function and vasoactive hormone systems in healthy subjects

The acute effects of i.v. somatostatin (250 mcg bolus followed by 250 mcg/h continuous infusion for two hours) on renal hemodynamics, renal electrolyte and water handling, and urinary excretion of catecholamines and prostaglandins, as well as on plasma concentrations of arginine vasopressin, atrial natriuretic factor, norepinephrine, epinephrine, dopamine, glucagon, and plasma renin activity were studied in seven normal subjects. Somatostatin decreased effective renal plasma flow and glomerular filtration rate, osmotic and free water clearances, urine volume, and sodium and potassium excretion, while urinary osmolality, fractional excretion of sodium, and phosphate excretion increased significantly. Plasma concentrations of arginine vasopressin, atrial natriuretic factor, norepinephrine, epinephrine, and dopamine remained unchanged, while plasma renin activity (3.0 +/- 0.25 vs 2.4 +/- 0.2 ng AngI/ml/h; p less than 0.01) and glucagon levels (40 +/- 11 vs 20 +/- 16 pg/ml; p less than 0.01) decreased. Urinary excretion of norepinephrine, epinephrine, dopamine, PGE2, and PGF2 alpha was suppressed under somatostatin. A significant positive correlation was found between urinary dopamine and sodium excretion (r = 0.7; p less than 0.001) and urinary prostaglandin E2 and glomerular filtration (r = 0.52; p less than 0.01). Without accompanying changes in plasma osmolality and vasopressin concentration significant antidiuresis occurred, suggesting a direct tubular effect of somatostatin. However, the hormone-induced changes are due mainly to the decrease in renal plasma flow. The results demonstrate that somatostatin at supraphysiological doses exerts significant effects on the kidney.

Cisplatin nephrotoxicity

Cisplatin is used widely in the treatment of a large number of carcinomas. The clinical use of cisplatin, however, can be complicated by myelotoxicity, ototoxicity and intestinal toxicity; we review briefly cisplatin nephrotoxicity. The principal route of its excretion is via the kidney, and accumulation of cisplatin in the renal cortex has been demonstrated. Three to five days following administration of cisplatin to rats, degenerative changes appear in the proximal tubule, including cytoplasmic vacuolization, tubular dilatation and pyknotic and hydropic degeneration. A decrease in renal plasma flow was observed very early on in patients receiving cisplatin at a dose of 20 mg/m 2 over a period of 4 h, and an increase in urinary enzymes occurred rapidly. Hypomagnesaemia, hypocalcaemia and hypokalaemia were frequent. The mechanism of cisplatin nephrotoxicity remain unclear. Biotransformation of cisplatin could play an important role; a decrease in sulphydryl groups in the kidney may be a primary event, and reactive metabolites may be formed. The incidence of cisplatin nephrotoxicity has been observed to decrease when patients are prehydrated, and it was proposed recently that administration of a calcium blocker might reduce the nephrotoxic effects of cisplatin. The clinical recommendations are to avoid rapid cisplatin infusion rates (over 1 mg/kg per hour) and to induce hydration at least during and after cisplatin administration. New compounds with the same or better antitumour activity and less toxicity should be prepared. At present, carboplatin appears to be preferable to cisplatin because of the reduced incidence of untoward effects.

Role of the Renin-Angiotensin System in the Regulation of Glomerular Filtration

Angiotensin II (Ang II) controls renal plasma flow, which depends on perfusion pressure and on renal vascular resistances; the glomerular filtration rate of single nephrons (SNGFR) also depends on these two parameters. The glomerulus can synthesize all components of the renin-angiotensin system. Renin is produced by mesangial cells and cells of afferent arterioles, angiotensinogen by mesangial cells, and angiotensin I-converting enzyme (ACE) by endothelial and mesangial cells. Ang II binds to afferent and efferent arterioles and to mesangial cells, which subsequently contract and enhance their production of vasodilator prostaglandins. Ang II participates in the regulation of the SNGFR by acting on arteriolar resistance, on the glomerular capillary surface area, and finally on the ultrafiltration coefficient. The synthesis of renin is initiated when the cAMP concentration increases under the influence of hormones (parathyroid hormone, catecholamines), of mediators (e.g., prostanoids), or of changes in composition of tubular fluid (in sodium, chlorine, or calcium) detected by the macula densa. Moreover, renin synthesis is stimulated by decreases in intracellular calcium concentration. The renin-angiotensin system plays an important role in the regulation of glomerular filtration. A decrease in renal plasma flow is followed by an increase in glomerular efferent arteriole resistance, so that perfusion pressure and glomerular filtration remain constant. Furthermore, if the decrease in renal plasma flow is more marked, vasodilator prostaglandins, whose synthesis is stimulated by Ang II, dilate afferent arterioles, which sustains glomerular filtration. Prostaglandins are also apt to bind to the juxtaglomerular apparatus and to increase the intracellular cAMP level.(ABSTRACT TRUNCATED AT 250 WORDS)

Captopril in patients with type II diabetes and renal insufficiency: Systemic and renal hemodynamic alterations

Purpose: To our knowledge, clinical studies on the long-term use of angiotensin converting enzyme inhibitors in patients with type II diabetes mellitus and nephropathy with incipient renal failure are nonexistent. We therefore assessed the effects of long-term treatment with captopril on systemic and renal hemodynamics and urinary protein excretion in patients with type II diabetes mellitus and the clinical syndrome of diabetic nephropathy. Patients and methods: Twelve patients, 10 men and two women, with an average age of 52 years (range, 40 to 66), participated in the study. After the basal hemodynamic evaluation, the patients received captopril in two daily doses. The dosage was adjusted at weekly intervals in order to obtain normalization of blood pressure without exceeding the maximum allowable dosage. Four patients also received furosemide (20 to 40 mg/day). Results: After six months of treatment, the intra-arterial blood pressure fell (from 162 ± 17 103 ± 5 to 139 ± 26 89 ± 10 mm Hg) due to the reduction in total peripheral vascular resistance index (from 3,720 ± 658 to 3,190 ± 762 dynes/second/cm −5/m 2), with no change in cardiac index (2.78 ± 0.36 to 2.79 ± 0.47 liters/minute/m 2). No significant change was seen in renal vascular resistance (from 30,175 ± 5,371 to 30,173 ± 5,372 dynes/second/cm −5/1.73 m 2) and in filtration fraction (from 26 ± 8 to 27 ± 10 percent). A slight, not significant, decrease in renal plasma flow (from 243 ± 97 to 217 ± 108 ml/minute/1.73 m 2), in glomerular filtration rate (from 57 ± 17 to 51 ± 19 ml/minute/1.73 m 2), and in proteinuria (from 4.50 ± 3.10 to 3.40 ± 2.31 g/day) was also observed. Conclusion: Our findings suggest that captopril is an effective antihypertensive agent in patients with diabetic nephropathy, but the renal beneficial effects seem to be limited when this syndrome is complicated by renal insufficiency.

Diuretic therapy in congestive heart failure for the elderly patient.

The incidence of congestive heart failure (CHF) in the elderly increases with age as 80% of patients hospitalised with CHF are older than 60 years of age. In this age group CHF may result from several factors such as coronary artery disease, hypertension, valvular disease or intrinsic myocardiopathies. Important alterations of renal physiology have been observed in this condition: decreases in renal plasma flow and glomerular filtration rate, and increases in renal venous pressure. Natriuretic hormone inhibition occurs and renin-angiotensin-aldosterone system activation and antidiuretic hormone secretion increase, resulting in positive water and sodium balances that contribute to the manifestations of congestive heart failure. The treatment of CHF in the elderly is similar to that in younger patients; the difference in management is determined by the severity of the disease and the side effects of the drugs used. Diuretics increase water and sodium elimination by the kidney and increase the systolic volume of the left ventricle, probably by the reduction of preload and afterload. Diuretic therapy must be pursued carefully in patients receiving digitalis, especially in those elderly individuals who may be on restricted diets: the most common adverse effects of diuretics in this age group are hypovolaemia, hyponatraemia, hypokalaemia and hypomagnesaemia.

Atrial natriuretic peptides: Reproducibility of renal effects and response of liver blood flow

To assess the variability of the response to exogenous atrial natriuretic peptide (ANP), it was infused at the rate of 1 microgram/min for 2 h in 6 salt-loaded normal volunteers under controlled conditions on 2 occasions at an interval of 1 week. The effect on solute excretion and the haemodynamic and endocrine actions were highly reproducible. The constant ANP infusion caused a delayed and prolonged excretion of sodium, chloride and calcium, no change in potassium or phosphate excretion or in glomerular filtration rate but a marked decrease in renal plasma flow. Blood pressure, heart rate and the plasma levels of angiotensin II, aldosterone, arginine vasopressin and plasma renin activity were unaltered. The effect of a 2-h infusion of ANP 0.5 microgram/min or its vehicle on apparent hepatic blood flow (HBF) was also studied in 14 normal volunteers by measuring the indocyanine green clearance. A 21% decrease in HBF was observed in subjects who received the ANP infusion (p less than 0.01 vs vehicle). Thus, ANP infused at a dose that did not lower blood pressure decreased both renal and liver blood flow in normotensive volunteers. The renal and endocrine responses to ANP were reproducible over a 1-week interval.

Renal Hemodynamic Abnormalities in Patients with Short Term Insulin-Dependent Diabetes Mellitus: Role of Renal Prostaglandins*

To determine if renal functional alterations in diabetes mellitus could be related to disturbances of vasoactive systems, renal plasma flow (RPF), glomerular filtration rate (GFR), PRA (basal and stimulated), plasma catecholamine levels, and urinary excretion of prostaglandin E2 (PGE2), 6-keto-PGF1 alpha, and kallikrein were determined in 21 patients with insulin-dependent diabetes mellitus (IDDM) of short duration and 15 normal subjects. In 7 additional patients with IDDM and in 4 normal subjects, the effect of lysine acetylsalicylate (LAS; 450 mg, iv) on GFR and RPF was studied. Patients with IDDM had higher RPF and GFR than normal subjects. Plasma norepinephrine and basal and stimulated PRA were significantly lower in IDDM than in the control group [161 +/- 82 (+/- SD) vs. 243 +/- 114 pg/ml, 0.19 +/- 0.20 vs. 1.15 +/- 0.33 ng/ml X h, and 0.93 +/- 0.82 vs. 2.8 +/- 1.73 ng/ml X h, respectively). No significant differences were found in the urinary excretion of PGE2, 6-keto-PGF1 alpha, and kallikrein in the two groups. LAS administration significantly reduced RPF (from 641 +/- 72 to 535 +/- 38 ml/min X 1.73 m2) and GFR (from 168 +/- 25 to 150 +/- 18 ml/min X 1.73 m2) in patients with IDDM, but not in normal subjects. In IDDM patients, there was a close direct correlation between the percent decrease in RPF and GFR induced by LAS and the baseline values of these parameters. The results suggest that in IDDM, there may be an imbalance between the degree of activation of the renin-angiotensin and sympathetic nervous systems and the renal production of PGs. The observation that LAS administration reduced RPF and GFR in these patients suggests that renal PGs are involved in the renal hyperperfusion of IDDM.

The effects of sar1ala8-angiotensin II in vasopressin-treated dehydrated sheep.

Mildly dehydrated conscious Merino ewes were infused with vasopressin (AVP) at 5 mu x min-1 alone and simultaneously with the angiotensin II receptor blocker sar1ala8-angiotensin II (saralasin) at 15 micrograms x min-1. AVP was slightly pressor and produced an increase in the calculated total peripheral resistance, and an increase in glomerular filtration rate, urine flow and electrolyte excretion, without a change in total renal plasma flow. These results indicate renal efferent arteriolar vasoconstriction as well as other non-renal vasoconstriction. Saralasin infusion checked the rise in total peripheral resistance (which continued to increase after saralasin withdrawal), but caused a marked increase in renal vascular resistance resulting in a decrease in renal plasma flow and to a lesser extent in glomerular filtration rate. These results suggest that saralasin was acting as an angiotensin II agonist in the kidney, but as an antagonist elsewhere. Deductions from previous experiments in the literature of the renal function of angiotensin II, based on its supposed inhibition by saralasin, may not be justified.

Effect of experimental acute renal failure on intrinsic renal tubular secretory clearance of organic cations in rats.

Effect of experimental acute renal failure (EARF) on the intrinsic renal tubular secretory clearance (CLscnint) of tetraethylammonium bromide (TEA) and N1-methylnicotinamide (NMN) was examined in rats treated with glycerol, folate, salicylate, uranium and gentamicin. The values of CLscnint was calculated by an equation incorporating the determinants of the renal clearance (CLr), i.e., renal tubular secretory clearance (CLscnr), glomerular filtration rate (GFR), renal plasma flow (RPF), free fraction of the drug in plasma (fp) and fraction (Freabs) of the drug reabsorbed after filtration and secretion in the urine. In the EARF-rats, the values of CLscnint of NMN and TEA were decreased by 0.017-0.575 times and by 0.005-0.737 times as compared to those of the normal rats, respectively. It was suggested that the decreases in CLscnr of both NMN and TEA were due not to the decrease in RPF, but to that in CLscnint.

The effect of intravenous insulin infusion on kidney function in insulin-dependent diabetes mellitus.

Glomerular filtration rate, renal plasma flow, urinary excretion of β-2-microglobulin and albumin, heart rate and blood pressure were studied in eight young male insulin-dependent diabetics. Measurements were performed before and during insulin infusion at 2 mU/kg/min. No patient had discernible insulin antibodies. Two studies were performed at random in each patient. In series A blood glucose concentration was allowed to decline, while in series B it was maintained at a constant level. Ten 20 min clearance periods were performed, four before and six during insulin infusion. Results are given as mean±SEM of values from the first four (control) and last four (test) clearance periods. Blood glucose declined in series A experiments from 10.8±0.8 mmol/l in the control period to 5.8±0.5 mmol/l during the test period, but remained constant during experiment B (9.8±1.1 and 9.5±1.1 mmol/l). Plasma insulin levels were comparable in the two series. Glomerular filtration rate fell from 141±7 ml/ min X 1.73m2 to 132±7ml/min X 1.73m2 (p< 0.01) in series A but did not change significantly during series B. Similarily renal plasma flow declined with declining glucose but remained constant when glucose was maintained at a constant level. In series A the magnitude of decrease in renal plasma flow was correlated with the magnitude of decrease in glomerular filtration rate (r=0.95, p< 0.001). β-2-microglobulin excretion decreased significantly (p < 0.05) in both series (A: 89±17 to 60±13 ng/min, B: 117±46 to 62±17ng/min). Albumin excretion increased in five out of six patients with normal control values (not significant) in series A and in four out of six in series B. No significant changes in heart rate or blood pressure were observed. Thus insulin infusion reduced renal plasma flow and glomerular filtration rate, but this effect could be completely abolished by keeping blood glucose constant. This suggests that it is not the lack of insulin but the associated hyperglycaemia which contributes to the elevated renal plasma flow and glomerular filtration rate in insulin-dependent diabetics.

Renal function during reflexly activated catecholamine flow through an adrenorenal rete

Reflex vasoconstriction that occurs in the kidney of the dog can be the result of either of two mechanisms. The first is by activation of the renal sympathetic nerves and the second by reflex activation of catecholamine flow through an adrenorenal rete. Both reflex mechanisms can be activated by transient hypotension caused by experimentally induced atrial fibrillation in the sodium-replete pentobarbital-anesthetized dog. This study was undertaken to measure and compare the magnitude of changes in renal function that occur when these reflex mechanisms are activated and to evaluate the possible role of intrarenal angiotensin II in these two reflex effects. Reflex activation of catecholamine flow through an adrenorenal rete in intact or denervated kidneys produced a 26 +/- 3% decrease in renal plasma flow, a 23 +/- 4% decrease in glomerular filtration rate, a 58 +/- 7% decrease in urinary sodium excretion, and a 4 +/- 1% increase in filtration fraction, but no change in the fractional distribution of intrarenal blood flow. Changes of a similar direction and magnitude were seen in the same animals during reflex activation of the renal sympathetic nerves in the kidneys with intact or ligated adrenorenal rete. The same studies were performed after the intrarenal action of angiotensin II was blocked with [Sar1,Ala8]angiotensin II and similar responses were seen. Both of these reflexes appear to be important mechanisms by which the kidney can maintain vascular volume, and neither depends on intrarenal angiotensin II activity.

Is low urinary prostaglandin concentration a stage in the development of essential hypertension?

Urinary prostaglandin E and F (PGE and PGF) concentrations, renal plasma flow (RPF), glomerular filtration rate (GFR), sodium excretion rate (UNaV), potassium excretion rate (UKV), urinary osmolarity (Uosm) and osmolar clearance (Cosm) were found to be higher, while mean blood pressure (MBP) was lower in a group of 15 normotensive subjects ( 15NS), compared to those values obtained in a group of 25 essential hypertensive patients (25EHP) of the same mean age. After volume expansion, of the 25EHP, urinary PGE concentration, RPF, noncortical plasma flow (NCPF), UNaV, UKV, UNaV/UKV, Cosm and urine volume (UV) increased significantly, MBP, GFR, Uosm, free water reabsorption (T c water) and urinary aldosterone concentration did not change, while plasma renin activity (PRA) decreased significantly. It was concluded that the deficiency in renomedullary PG synthesis in the EHP is accompanied by a decrease in RPF, NCPF and UNaV. This decrease in UNaV and renal hemodynamics could increase, in the long term, the BP in these patients. Nevertheless, these findings do not exclude the interpretation that the decrease in renomedullary PGE release in the EHP indicates an attempt to increase sodium excretion at the distal tubule by diminishing sodium reabsorption by this agent in order to prevent further increase in BP. In any case, it seems that renomedullary PGs play an important role in intra-renal control systems.

Alterations in Renin Release by PGE&lt;sub&gt;2&lt;/sub&gt; and Acetylcholine in Indomethacin-Treated Dogs

We evaluated the effect of intrarenal vasodilatation on renin release in the indomethacin (2 mg/kg) treated pentobarbital anesthetized dog. Pretreatment with indomethacin resulted in a significant decrease in renal plasma flow (RPF) without change in glomerular filtration rate (GFR). Intrarenal infusion of prostaglandin E&lt;sub&gt;2&lt;/sub&gt; (PGE&lt;sub&gt;2&lt;/sub&gt;, 2 µg/min) and acetylcholine (ACh, 40 µg/min) completely restored RPF in these dogs. Following PGE&lt;sub&gt;2&lt;/sub&gt; administration a significant increase in absolute sodium excretion (UNaV), renal vein renin activity (RVRA), and renin secretory rate (RSR) were observed. Despite similar effects on RPF and UNaV, acetylcholine did not alter renin release as measured by plasma renin activity (PRA), RVRA or RSR. These results show that vasodilatation alone is not the mechanism by which exogenous PGE&lt;sub&gt;2&lt;/sub&gt; increased renin release during cyclo-oxygenase inhibition.