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Biomedical subjects

A A Attallah

Publications and source records attributed to A A Attallah.

At least 19 recordsLinked to original sources

Captopril reduces renal excretion of prostaglandin E2 in the sodium-depleted rabbit.

The effects of captopril on renal function and prostaglandin E2 excretion were investigated in rabbits undergoing chronic sodium depletion. Captopril administered for six days, via rate-controlled osmotic pumps, caused diuresis and marked natriuresis which were accompanied by a significant reduction of urinary prostaglandin E2 excretion and of glomerular filtration rate. It is concluded that captopril reduces the renal excretion of prostaglandin E2 and that its diuretic and natriuretic effects are prostaglandin E2-independent.

Animals↗

The effect of sodium intake on rabbit renal prostaglandin E2 and thromboxane A2: dissociation from the renin-angiotensin system.

The effects of chronic alterations in dietary sodium intake on urinary prostaglandin (PG) E2 and thromboxane (TX) B2 was investigated in the rabbit. Sodium restriction, over a 15-day period, reduced daily urinary PGE2 and TXB2 in concordance with urinary flow (V) and sodium excretion (UNa+V), but increased plasma renin activity (PRA) and plasma aldosterone concentration (PAC). Sodium repletion, on the other hand, increased urinary PGE2 and TXB2 in proportion to the rise in V, but reduced PRA and PAC. During both sodium diets PGE2 and TXB2 correlated positively with V and negatively with PRA. It is concluded that chronic sodium intake produces opposite changes in the renal prostaglandin and the renin-angiotensin systems.

Aldosterone↗

Effect of Sar1-Ileu8-angiotensin on renal prostaglandin E2 biosynthesis and excretion.

To test the hypothesis that renal prostaglandin (PG) biosynthesis is regulated by angiotensin (AII), rabbits were given prolonged treatment with the AII analogue, Sar1-Ileu8AII (200 micrograms/kg/4 hr, subcutaneously), for 2 days during a low, normal, and high sodium intake. Sodium restriction augmented plasma renin activity (PRA), which was associated with a rise in basal renal PGE2 synthesis and urinary excretion, whereas sodium supplementation attenuated PRA with a decrease in renal PGE2 synthesis and urinary excretion. Sar1-Ileu8AII administration, with either a low, normal, or high salt intake, suppressed PRA. Sar1-Ileu8AII injection with a low sodium intake also suppressed renal PGE2 synthesis and excretion that was associated with a fall in blood pressure, suggesting an antagonistic action of this agent on vascular beds and renal PGE2 synthesis. On the other hand, with a high sodium intake Sar1-Ileu8-AII increased renal PGE2 synthesis and excretion as well as blood pressure, revealing an agonistic action of this compound under these conditions. The results suggest that exogenous AII analogue may act as an antagonist or agonist depending on sodium intake and endogenous AII levels, renal PGE2 synthesis is dependent on AII levels, either endogenously produced or exogenously administered (as an AII agonist), and the action of AII analogue on vascular beds and renal PGE2 synthesis does not appear to parallel its action on renin-AII feedback regulation at the juxtaglomerular cell especially under conditions of high sodium intake.

1-Sarcosine-8-Isoleucine Angiotensin II↗

Lack of effect of verapamil on urinary prostaglandin E2 excretion in the rabbit.

The effects of verapamil on renal function, the renin-angiotensin-aldosterone system and renal prostaglandin E2 were investigated in the rabbit. Verapamil, administered with rate-controlled osmotic pumps, showed no significant effects on plasma renin activity, plasma aldosterone and urinary prostaglandin E2 excretion. There were marked rises in the glomerular filtration rate and calcium excretion but no significant change in slat and water excretion was observed with verapamil. It is concluded that the hypotensive response to verapamil is unrelated to the renin-angiotensin-aldosterone system and to renal prostaglandin E2.

Alprostadil↗

Mechanism of furosemide-induced natriuresis by direct stimulation of renal prostaglandin E2.

Studies were conducted to investigate the interaction of renal prostaglandin E2 (PGE2) production and the renin-angiotensin system in the mechanism of furosemide-induced natriuresis. In conscious rabbits with permanent urinary bladder cannulation, furosemide in vivo (10 mg/kg) increased urinary water, sodium, and PGE2 excretion and plasma renin activity (PRA) over 50 min. Furosemide administered in vivo enhanced renal papillary but not cortical in vitro PGE2 biosynthesis. Prior administration of indomethacin at 2 mg/kg augmented the saluretic effect of furosemide, decreased its effect on UPGE2 V, abolished the rise in PRA, and reduced cortical but not papillary PGE2 biosynthesis. However, at 10 mg/kg, indomethacin reduced the saluretic effect of furosemide and eliminated the increase in UPGE2 V with continued suppression of PRA. Direct addition of furosemide in vitro to the incubation medium (10(-5) and 10(-3) M) markedly augmented papillary PGE2 synthesis. It is concluded that furosemide stimulates renal papillary PGE2 biosynthesis directly without mediation by angiotensin II, resulting in an increase in UPGE2 V, and the enhanced or inhibitory effect of indomethacin on furosemide-induced natriuresis is dose related and dependent on the degree of PGE2 synthesis inhibition in the presence of suppressed PRA, which occurred at all doses studied.

Angiotensin II↗

Renal prostaglandin E2 biosynthesis: dependence on angiotensin II.

To study the interaction of the prohypertensive renin-angiotensin axis with the antihypertensive renal prostaglandins, angiotensin-converting enzyme inhibition (captopril and teprotide) and angiotensin blockade (Sar1-Ile8-AII) were produced in rabbits in vivo and renal slice prostaglandin E2 was measured in vitro after 30 minutes of incubation in Krebs-Ringer HCO3- buffer. In rabbits with angiotensin-converting enzyme inhibition, de novo prostaglandin E2 synthesis decreased in cortical, outer medullary and papillary slices by 85, 52 and 47 percent, respectively. Similar degrees of inhibition were observed with angiotensin blockade. It is concluded that renal prostaglandin E2 synthesis is angiotensin II dependent under these conditions. This finding suggests that any increase in the prohypertensive antinatriuretic renin-angiotensin axis may be associated with a secondary increase in renal prostaglandin E2 which may be acting in an antihypertensive natriuretic compensatory fashion.

1-Sarcosine-8-Isoleucine Angiotensin II↗

Inhibition of rabbit renal prostaglandin E2 biosynthesis by chronic potassium deficiency.

To test the hypothesis that renal PGs may mediate the renal functional defect of potassium depletion, rabbits were placed on normal potassium and potassium-deficient diets for 7 weeks, and measurements were made of urinary PGE2 excretion; renal cortical, medullary, and papillary PGE2 content; and in vitro, de novo PGE2 biosynthesis. In the sixth week maximal urinary osmolality declined significantly, from 1118 +/- 44 mOsm/kg of H2O in controls to 666 +/- 25 in potassium-deficient animals, accompanied by a corresponding decrease in urinary excretion of potassium from 12.2 +/- 0.7 mEq/24 hr to 0.93 +/- 0.1 and in muscle potassium content from 39.0 +/- 1.0 mEq/100 gm to 22.3 +/- 1.9. By 3 weeks urinary excretion of PGE2 was significantly lower in hypokalemic animals than in controls. Renal cortical, medullary, and papillary PGE2 tissue content decreased significantly, from 0.061 +/- 0.01 microgram/gm to 0.022 +/- 0.005, 0.73 +/- 0.09 microgram/gm to 0.267 +/- 0.036, and 8.6 +/- 1.04 microgram/gm to 4.6 +/- 1.4, respectively. In vitro PGE2 biosynthesis by cortical, medullary, and papillary slices from normal animals was 0.102 +/- 0.01, 9.55 +/- 1.7, and 25.5 +/- 2.8 microgram/gm/30 min, whereas corresponding values from hypokalemic rabbits were 0.04 +/- 0.006, 3.9 +/- 0.747, and 14.0 +/- 1.25 microgram/gm/30 min, respectively. These results indicate that renal slices from hypokalemic rabbits synthesize much less PGE2 in vitro than do normal controls. The date do not support the hypothesis that enhanced PGE2 synthesis mediates the renal concentrating defect of chronic potassium deficiency but suggest that decreased renal PGE2 production may underlie the impairment in renal hemodynamics known to exist in this condition.

Animals↗

Sar1-Ile8-angiotensin II decreases urinary PGE2 and PGF2alpha excretion in rabbits on dietary sodium restriction.

Urinary PGE2 and PFG 2 alpha excretion (UPGV) were determined prior, during and after 48 h treatment with angiotensin-II-blocker, Sar1-Ile8-angiotensin II (200 microgram/kg/3 h), in rabbits maintained on chronic low (LS) or high (HS) salt diets. UPGE2V and F2 alpha were significantly (P < 0.001) higher in LS than in HS. Sar1-Ile-8-angiotensin II decreased the elevated UPGE2 V and UPGF2 alpha V in LS from 2.60 +/- 0.084 microgram/24 h to 1.13 +/- 0.21 microgram/24 h and from 6.63 +/- 0.61 to 3.77 +/- 0.86 microgram/24 h respectively. In animals with HS intake, angiotensin II blockade failed to effect urinary prostaglandin excretion.

1-Sarcosine-8-Isoleucine Angiotensin II↗

Indomethacin, salicylates and prostaglandin binding.

Aspirin, salicylic acid and indomethacin reversibly inhibit prostaglandin binding to human serum proteins. This effect was demonstrated in the sera of normal subjects and of rheumatoid arthritis patients treated with aspirin as well as by addition of these drugs to serum in vitro. The displacement of serum prostaglandins by salicylate is likely to affect the kinetics of prostaglandin transport and may facilitate the delivery of prostaglandins from serum to tissue receptors.

Arthritis, Rheumatoid↗

Antidiuresis and inhibition of PGE2 excretion by hyperoxia in the conscious dog.

Experiments were performed to determine the influence of varying inspired oxygen tension on renal prostaglandin E2 (PGE2) excretion, renal hemodynamics, and water and electrolyte excretion in the conscious dog. Hypoxic exposure (PIO2 = 56 torr) resulted in a 13% increase in renal blood flow (RBF), while hyperoxic breathing with PIO2 of 700, 1426, or 2139 torr, all resulted in significant 5--7% decline in RBF, a response that was significantly attenuated compared to the striking renal vasoconstriction caused by hyperoxia in anesthetized dogs. Hyperbaric oxygenation (HBO) (1426 torr O2, 2139 torr O2) was associated with unexpected decreases in urine flow (V) of 61% and 70%, respectively. The antidiuresis and mild hemodynamic adjustments were correlated with a 67% decline in urinary PGE2 excretion (UPGE2 x V) when the dogs breathed 700 torr O2, while exposure to 1426 torr O2 and 2139 torr O2 diminished UPGE2 x V by 92% and 99%, respectively. Plasma antidiuretic hormone (ADH) concentration, measured during exposure to 1426 torr O2, was unchanged. In addition, this nonpharmacologic hyperbaric decline in PGE2 excretion was not associated with any changes in sodium excretion of renin secretion, in contrast to the usual depression of these variables with pharmacologic PG inhibition (indomethacin). The HBO antidiuresis may be a consequence of an increased medullary osmotic gradient secondary to reduced vasa recta blood flow. Alternatively, this antiduresis could occur as a consequence of a lowering of the normal functional antagonism existing between PGE2 and ADH, such that the influence of endogenous ADH is potentiated.

Animals↗

Stimulation of rabbit renal PGE2 biosynthesis by dietary sodium restriction.

Immunoreactive prostaglandin E2 (PGE2) was measured in slices of renal papilla (P), outer medulla (OM), and cortex (C) before and after 30 min of incubation (biosynthesis) in Krebs-Ringer HCO3- buffer in rabbits on low (LS), normal (NS), and high (HS) sodium diets. The 24-h urine PGE2 was also measured daily for 10 days prior to incubation. Daily urine PGE2 was significantly higher (911 +/- 54 ng) in LS, decreasing to 605 +/- 33 at NS, and 558 +/- 48 ng at HS, Initial slice PGE2 was highest in P at LS (35.5 +/- 5.1 MICROGRAMS/G), 5.1 microgram/g), decreasing to 16.9 +/- 1.3 at NS and 18.0 +/- 2.6 micrograms/g at HS. Similar patterns were observed in OM and C, which were quantitatively much lower. PGE2 biosynthesis was highest at LS (P, 139 +/- 21; OM, 58.8 +/- 5.1; C, 0.20 +/- 0.05 micrograms.G-1.30 Min-1) and lowest at HS (P, 58.9 +/- 7.4; OM, 11.8 +/- 3.1; C, 0.07 +/- 0.01 micrograms.g-1.30 min-1). Although PGE2 concentration was higher in P than in OM, the percent increase in OM PGE2 biosynthesis on LS was 3--4 times greater than in P. Since OM is 28% and P is 2% of total renal mass, these results indicate that LS markedly stimulates PGE2 biosynthesis primarily in OM and to a lesser extent in P and C, findings suggesting an important role for OM PGE2 in the renal adaptation to sodium deprivation.

Animals↗

Renal biosynthesis of prostaglandin E2 and F2alpha: dependence on extracellular potassium.

Since recent investigations have shown elevated urinary PGE2 and polyuria in hypokalemic animals which were reversed by PG synthesis inhibition with indomethacin, studies were undertaken to examine the effects of extracellular [K+] on renomedullary PG production in vitro. Slices of rabbit and human renal papilla were incubated in Krebs-Ringer HCO3- buffer, 95% O2-5% CO2, glucose 10 mM, HSA 4 gm/100 ml, for 30 min at 38 degrees C, with and without 1-14C-AA (10 micrometer). Measurments were made of total endogenous iPGE2 and iPGF2alpha production and radioactive AA leads to PGE2. In rabbit renal medulla values for iPGE2 (nmol/gm/30 min) were 252 +/- 20 at [K+] 0; 182 +/- 17 at [K+] 2.5 mEq/L; 163 +/- 18 at [K+] 5.5; and 129 +/- 17 [K+] 9.0 (p less than 0.005). iPGF2alpha was unaltered by changes in media potassium concentrations (6.8 +/- 0.9 nmol/gm/30 min at [K+] 0 and 6.2 +/- 0.8 at [K+] 9.0 MEq/L). In the human renal medulla iPGE2 was 9.5 +/- 1.6 nmol/gm/30 min at [K+] 0; 5.0 +/- 0.7 at [K+] 2.5 mEq/L; 5.3 +/- 0.3 at [K+] 5.5; and 4.6 +/- 1.0 at [K+] 9.0 (p less than 0.05). AA leads to PGE2 (nmol/gm/30 min) was 3.21 +/- 0.92 at [K+] 0; 2.47 +/- 0.57 at [K+] 2.5 mEq/L; 1.30 +/- 0.30 at [K+] 5.5; and 0.76 +/- 0.4 at [K+] 9.0 in rabbit medulla (P less than 0.005). It is postulated that direct stimulation of papillary PGE2 biosynthesis by low extracellular [K+] impairing the cAMP-generating response to vasopressin could represent the initial event in the pathogenesis of vasopressin-resistant polyuria.

Animals↗

Renal prostaglandins.

The renal prostaglandins PGS2 and PGE2 possess potent antihypertensive and vasodepressor activity. The mechanism of blood pressure lowering effect is through peripheral arteriolar dilation with a fall in total peripheral resistance. PGA unlike PGE escape degradation by the lung and thus could circulate as antihypertensive hormones. Since plasma PGA levels rise in humans on a low sodium intake, it has been postulated that the beneficial effects of a low sodium diet in some hypertensives may be the result of an increase in peripheral vasodilating PGA. Support that plasma PGA may be a regulator of systemic blood pressure is also derived from the fact a PGA-secreting renal tumor was associated with a fall in blood pressure and a rise in plasma PGA in a previously hypertensive woman. The removal of the tumor resulted in a return of blood pressure to elevated levels and a concomitant fall in PGA. Recently, a number of human patients with essential hypertension have been infused with PGA1 and PGA2. It was observed that there was an initial increase in renal blood flow, sodium and water excretion which was associated with no change in the elevated blood pressure. When blood pressure ultimately fell, there was a return of renal blood flow, sodium and water excretion to preinfusion levels. It would appear that PGA compounds act as 'ideal' antihypertensive agents since they favorably effect renal resistance, sodium and water homeostasis, plasma volume, total peripheral resistance, blood pressure and indirectly cardiac output through baroreceptor stimulation, all factors known to be important in etiology in human hypertension.

Animals↗