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Biomedical subjects

H Eliahou

Publications and source records attributed to H Eliahou.

18 recordsLinked to original sources

Expression of opioid receptors during heart ontogeny in normotensive and hypertensive rats.

BACKGROUND: The opioidergic systems are involved in modulating nociceptive stimuli. In addition, the recent results suggest that endogenous and exogenous opioids could play a role in the modulation of blood pressure and cardiac functions. However, little is known regarding the expression and role of opioid-binding sites in the heart. The decreased sensitivity to noxious stimuli in hypertensive rats raises the possibility of different developmental pattern expression of opioid-binding sites in normotensive versus hypertensive rats. METHODS AND RESULTS: Opioid receptor expression in hearts from hypertensive and normotensive rats was studied during heart development by binding assays. From P1 until P90, the development of the heart in the two rat strains was accompanied by a gradual increase in the density of kappa-opioid receptors. Hearts from hypertensive rats expressed significantly higher levels of kappa receptors compared with those of normotensive rats. At ages older than P7, mu-opioid receptors could not be detected in hearts of both strains, whereas delta-opioid-binding sites gradually increased until reaching adult levels. Seven-day-old cardiomyocyte cultures of both rat strains expressed similar densities of delta or kappa receptors to those observed in hearts from 7-day-old neonates. The mu-binding sites were not detected in cardiomyocytes cultures. Similar to the in vivo state, cultured myocytes from hypertensive rats had significantly higher levels of kappa-binding sites (1.5 fold) compared with those of normotensive rats. The kappa sites are pertussis toxin sensitive, and the state of coupling of the receptor to G protein is similar for the two rat strains. CONCLUSION: The role of opioid-binding sites in the heart is not completely clear. Hypertensive rats are known to be less sensitive to noxious stimuli compared with normotensive rats. It is controversial whether the site if application of noxious stimuli plays an important role in the sensitivity to pain in hypertensive rats. We suggest that the opioidergic system could play a role in the modulation of blood pressure in addition to its known effect on nociception.

Animals↗

Hyperinsulinaemia increases blood pressure in genetically predisposed spontaneously hypertensive rats but not in normotensive Wistar-Kyoto rats.

BACKGROUND: There is controversy in the literature concerning the effect of short-term insulin administration on blood pressure in different experimental situations, because in some experiments this association is clear, whereas in others it is nonexistent. OBJECTIVE: To investigate whether there is a difference in the effect of exogenous insulin administration on the blood pressure of normotensive Wistar-Kyoto (WKY) rats and hypertensive spontaneously hypertensive rats (SHR). METHODS: Hyperinsulinaemia was induced in normotensive WKY rats and in hypertensive SHR by the administration of long-acting insulin (insulin retard 0.4 U/kg body weight per day in one group and 0.8 U/kg body weight per day in another group) once a day, intraperitoneally, for 3 weeks. All of the rats drank a 10% sucrose solution, to prevent hypoglycaemia in those receiving insulin. RESULTS. Baseline serum levels were significantly higher in the SHR groups than in the WKY rat groups. At the end of the experiment, after 3 weeks' insulin therapy, systolic blood pressure measured by the tail-cuff method showed a significant increase in the SHR, but not in the WKY rats, possibly because of the genetic predisposition of the SHR to increase their blood pressure. The increase was similar in the SHR given 0.4 U/kg body weight per day insulin retard to that in those given 0.8 U/kg per day. CONCLUSIONS: Exogenous insulin increased systolic blood pressure in the SHR but not in the WKY rats. The rise was similar in rats receiving either 0.4 or 0.8 U/kg body weight per day insulin retard.

Animals↗

Normal renin-aldosterone-insulin and potassium interrelationship in FMF patients and amyloid nephropathy.

The renin-aldosterone system and plasma insulin were studied in 19 patients with familial Mediterranean fever (FMF). Their relationships to serum potassium level at rest and before and after oral glucose loading are described. An interesting finding is the occurrence of hyperkalemia in the absence of oliguria, in the advanced stages of renal failure. No differences were found in the activity of the renin-angiotensin-aldosterone system to explain these variations in serum potassium found in some of the patients. The response of the renin-aldosterone system to glucose loading showed no abnormality, and the regular relationship between serum potassium, plasma renin activity (PRA), aldosterone, insulin, and plasma pH is maintained. Levels of insulin, potassium, and bicarbonate in serum or plasma pH were found similar in FMF patients with normal renal function with and without proteinuria. Further decrease in renal function due to the progression of the underlying disease is manifested by an increase in FENa+ and FEK+ and a hyperchloremic metabolic acidosis, as is the case in other patients with chronic renal failure.

Adult↗

Receptor-cyclase coupling protein in erythrocytes of patients with essential hypertension.

In order to define the alteration of the function of the adrenergic system in hypertension, we studied directly the receptor-cyclase coupling protein (N protein), which is one of the components of the enzyme adenylate cyclase. N protein was determined in erythrocyte membranes of patients with essential hypertension and normal subjects, with a complementation assay in vitro. Fifteen normal subjects and 18 patients with essential hypertension (eight untreated and ten treated with beta-adrenoreceptor blocking drugs alone or in combination with other antihypertensive drugs), and two patients with pseudohypoparathyroidism type Ia (known to have deficient N protein activity), were studied. Erythrocyte N protein activities in the various groups expressed as percentages of the means +/- SD of normals were: normal subjects 100 + 13.7, untreated hypertensive 108.9 +/- 20.4, treated hypertensive 104.3 +/- 11.3 and pseudohypoparathyroidism type Ia 43%. The difference between N protein activity in the hypertensive patients and normals was not statistically significant. We suggest that the molecular basis for the altered sympathetic responsiveness in essential hypertension may reside in other components of the cyclic AMP protein kinase effector system.

Adolescent↗

Sodium, potassium and age: possible determinants of plasma renin activity and aldosterone during childhood (age 4-16).

The renin-angiotensin-aldosterone system was studied in fifty healthy children aged 4-16 years under normal sodium and potassium intake. The plasma renin activity (PRA) and plasma aldosterone (PA) decreased with age: r = -0.30, P less than 0.05 for plasma renin activity and r = -0.33, P less than 0.05 for plasma aldosterone. Significant negative correlation was obtained between plasma renin activity and the 24-h urinary sodium excretion; r = -0.40, P less than 0.01. This relationship remained significant when the daily urinary sodium excretion was corrected for 1.73 m2 body surface area (BSA); r = -0.40, P less than 0.01. Using the multivariance analysis, plotting the plasma renin activity against the two combined parameters (24-h urinary sodium excretion and age), no improvement was obtained (r = 0.38, P greater than 0.05). This finding suggests that during childhood, sodium rather than age has a major modulatory role on plasma renin activity. With advancing age the plasma aldosterone showed a significant positive correlation coefficient with plasma renin activity(r = 0.29, P less than 0.05). Multivariance analysis between plasma aldosterone and the two combined parameters, Plasma renin activity and age, significantly improved the correlation coefficient (r = 0.42, P less than 0.05) suggesting that both plasma renin activity and age play a dominant modulatory role in the control of plasma aldosterone during childhood. Neither 24-h urinary sodium excretion, nor 24-h urinary potassium excretion, improved the multiple correlation coefficient with plasma aldosterone when added to plasma renin activity and age.

Adolescent↗

beta 1-Adrenergic receptors in kidney tubular cell membrane in the rat.

We used a beta-adrenergic antagonist, (-) 3H-dihydroalprenolol, to demonstrate binding sites in purified rat kidney preparations that consistsed of plasma membranes of cells from tubules. The tubular origin of these plasma membranes was shown by electron microscopy and Na-K-ATPase enrichment. The binding was rapid (t1/2, 78 sec) and rapidly reversible (t1/2, 48 sec). The binding sites were saturable and bound 69.8 +/- (SD) 29.1 fmoles/mg of membrane protein. The binding was stereospecific with the isomers of beta-adrenergic agonists and beta-adrenergic antagonist propranolol, the (-) isomers being about 40 times more potent than the (+) isomers incompeting for these sites. (-) 3H-dihydroalprenolol had a high affinity for the binding sites, expressed by the mean equilibrium dissociation constant (KD) (KD, 7.1 nM). The beta-adrenergic antagonist (-) propranolol also showed high affinity (KD, 62.8 nM). The order of potency for inhibition of binding by beta-adrenergic agonists was: (-) isoproterenol (KD, 0.66 microM) greater than (-) epinephrine (KD, 4.3 microM) greater than or equal to (-) norepinephrine (KD, 13.5 microM). Conclusion. The (-) 3H-dihydroalprenolol binding sites in the rat kidney tubular cell membrane are beta-adrenergic receptor of the beta1 subgroup.

Alprenolol↗

Exercise tolerance in patients on chronic hemodialysis.

Twenty-two patients on chronic hemodialysis were tested on a bicycle ergometer to determine their near-maximal physical work capacity. The patients were found to have low physical work capacity that averaged 51.6 +/- 3.8 (SE)% predialysis and 50.3 +/- 3.7% postdialysis, when compared with the physical work capacity of healthy control subjects. The exercise was stopped when patients complained of muscular fatigue, and the work load at this point was considered their subjective maximal work capacity. At this stage the patients had high blood lactic acid levels and an increased double product (systolic blood pressure x heart rate), the latter indicating a high stage of cardiac output. The oxygen consumption and oxygen pulse were similar to those obtained from control individuals at the same work load. This study suggests that limited physical work capacity of chronic hemodialysis patients is due to early muscular fatigue. This phenomenon is associated with the rapid onset of anaerobic metabolism and may thus be caused by limited maximal oxygen uptake.

Adult↗

Postnatal changes in plasma and renal renin of the rat.

Plasma renin activity (PRA) of infant rats is high until some time between the 3rd and 4th week after birth. Mothers, however, return PRA to normal by 2 weeks post partum. The rate of disappearance endogenous PRA of nephrectomized rats is slower in those animals having gigh PRA than in mature rats. Disappearance curves of endogenous PRA of mothers post partum is also the same as that of normal mature females. Part of the high PRA of the neonate can thereby be the related to the lower rate of destruction. Total kidney renin content increases with age. Renal renin activity (RRA) is low only during the 1st postnatal week when expressed in terms of whole kidney weight and compared to later postnatal times. Although there are some slight differences in the means in older animals, none are statistically significant.

Age Factors↗

beta-Adrenergic blockade reduces the severity of acute renal failure in rats.

Propranolol administration in the hypoxic model of acute renal failure (ARF) in rats has reduced plasma renin activity (PRA) and uraemia as compared to untreated controls. P113 has no effect on uraemia but increased PRA in ARF. A combination of both drugs is no more effective in reducing uraemia than propranolol alone. These results support the view that beta-adrenergic blockade by propranolol reduces the severity of ARF by preventing the post-hypoxic release of renin.

Acute Kidney Injury↗

Acute renal failure in combat injuries.

The mortality in 25 patients suffering from post-combat injury acute renal failure (ARF) was 64%. Abdominal injuries were present in 17 patients with a mortality rate of 64.7%. Respiratory insufficiency occurred in 14 patients, jaundice occurred in 13, and septicemia in 10. The mean period of oliguria was high, 24.1 days per survivor, and the number of hemodialyses averaged 21.6 per survivor. It is concluded that the high mortality is primary due to the severity of the underlying injury itself and not due to the renal failure, that the ARF is more severe than in civilian injuries, as evidenced by a prolonged oliguric phase, and that frequent and intensive hemodialysis regimen is necessary for the elimination of deaths from uremia per se.

Acute Kidney Injury↗

Renoprotective effect of angiotensin II receptor antagonists in experimental chronic renal failure.

We compared the antihypertensive and renoprotective effects of the angiotensin II receptor antagonist losartan and the calcium channel blocker verapamil in the rat with chronic renal failure. One month after five-sixths nephrectomy, male WKY rats were treated for 2 months with either losartan or verapamil. Both resulted in a similar reduction in blood pressure: from 147.1 to 112 mm Hg in losartan-treated and from 155 to 118 mm Hg (p = NS) in verapamil-treated rats. Losartan improved the creatinine clearance (difference + 17.1% as compared with + 6.6% for verapamil, p = 0.039) and prevented the increase in proteinuria: 12.26 +/- (SE) 2.33 mg/day before and 18.48 +/- 2.19 mg/day (p = NS) after therapy in the losartan-treated and 17.27 +/- 2.73 mg/day before and 32.27 +/- 10.29 mg/day after therapy (p = 0.0484) in the verapamil-treated group. In addition, losartan resulted in minimal mesangial proliferation and significantly less glomerular sclerosis and thickening of the small arterial and arteriolar walls. The changes in interstitial fibrosis and tubular hypertrophy, however, were similar in both the verapamil- and losartan-treated groups. Treatment with losartan 1 month after five-sixths nephrectomy in male WKY rats resulted in reduced blood pressure, similar to that of the verapamil-treated group. However, despite similar antihypertensive properties, losartan improved creatinine clearance and reduced proteinuria. The losartan-treated group also had a marked reduction in mesangial proliferation and less glomerular sclerosis and less reduced vascular wall thickness in renal small arteries and arterioles. However, losartan did not totally eliminate nephrosclerosis. The tubular and interstitial changes were fewer in the losartan-treated group. Thus losartan has an additional, although only partial, renoprotective effect when compared with verapamil.

Angiotensin Receptor Antagonists↗