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Biomedical subjects

D Ben-Ishay

Publications and source records attributed to D Ben-Ishay.

At least 37 records · Page 2Linked to original sources
PubMed1991

Improved kidney function with cilazapril in hypertensive type II diabetics with chronic renal failure.

The purpose of this study was to determine efficacy and safety of the angiotensin converting enzyme inhibitor, cilazapril, in the treatment of hypertensive diabetics with renal insufficiency. Fifteen type II diabetics with hypertension and chronic renal insufficiency aged (mean +/- SD) 64 +/- 7 years were studied in a regional clinic and university hospital hypertension unit. The blood pressure was measured biweekly. Urinary collections were done after 2 weeks of placebo and 8 weeks of cilazapril treatment. The blood pressure decreased from 176 +/- 15/105 +/- 9 to 164 +/- 11/95 +/- 9 mm Hg and serum creatinine from 197 +/- 69 to 179 +/- 73 mumol/L. The creatinine clearance rose from 41.6 +/- 11.4 to 47.4 +/- 14.9 ml/min, while protein excretion decreased from 0.8 +/- 1.3 to 0.5 +/- 0.8 g/24 h (p less than 0.05). The blood pressure change was inversely correlated with the creatinine clearance change (r = -0.5, n = 15, p less than 0.05). In these high-risk patients, 8 weeks of cilazapril treatment improved both blood pressure control and renal function but renal function improved most in the patients whose blood pressure changed the least.

Aged↗
PubMed1991

Limitations of the captopril test in the diagnosis of renovascular hypertension.

The captopril test has been suggested as a sensitive and specific noninvasive tool for the diagnosis of renovascular hypertension. We applied the test to 72 consecutive hypertensive patients in whom renal artery stenosis was suspected. The test was positive in seven cases (9.7%), of whom four were true positive and three false positive. The captopril test has value in screening for renovascular hypertension, but its limitations should be recognized. False positive results are not uncommon and false negative results have been reported under certain circumstances. Nevertheless, when properly applied to appropriate patients, the test can enhance the diagnosis of renal artery stenosis.

Adolescent↗
PubMed1990

Cardiac hypertrophy developing during DOCA-salt treatment is dissociated from systemic and regional hemodynamics.

Systemic and regional hemodynamics were studied in DOCA-treated Sabra hypertensive (SBH) and normotensive (SBN) rats. In SBH rats, mean arterial pressure (MAP) and total peripheral resistance index (TPRI) increased significantly. In SBN rats, MAP remained stable and TPRI decreased. Cardiac output and heart rate were unchanged. Opposed changes in TPRI were mediated mainly by changes in vascular resistance of the skin, skeletal muscles and splanchnic organs. Both strains developed significant biventricular hypertrophy. We conclude that SBH and SBN rats' susceptibility or resistance to DOCA-salt hypertension are associated with opposed changes in TPRI. The development of biventricular hypertrophy is apparently dissociated from systemic hemodynamic changes.

Animals↗
PubMed1990

[Binding sites of imidazolines. Study with (3H)-idazoxan in renal cortex of Sabra salt-sensitive (SBH) and salt-resistant (SBN) rats].

Imidazoline binding sites have been characterized in organs modulating blood pressure, such as brain and kidney with (3H)-p-aminoclonidine and (3H)-Idazoxan respectively. However, the pharmacological characteristics of the imidazoline-preferring binding sites differ considerably depending on the species investigated and the radioligand used. Little is known about the physiological relevance of the non-adrenergic (3H)-idazoxan binding sites. As some imidazolines and certain alpha-adrenoceptor agonists possess antihypertensive activity, an alteration of these binding sites should be considered as a possible causes in the development of hypertension. In the present study, we performed binding studies with the imidazoline ligand (3H)-idazoxan in renal cortex of hypertensive salt-sensitive (SBH) and normotensive salt-resistant (SBN) Sabra rats. (3H)-idazoxan binding capacities were higher in SBH than in SBN rats. Competition studies have shown for (3H)-idazoxan specific binding non-adrenergic characteristics exclusively. In these both substrains, (3H)-idazoxan binding exhibit pharmacological profile of imidazoline binding sites. However, theses sites have also high affinity for guanidino compounds and amiloride. Surprisingly, amiloride and some analogues were significantly more potent in SBN than in SBH rats. From this study, it is difficult to elucidate the physiological role of imidazoline binding sites in renal cortex. However, differences observed between SBN and SBH suggest that these sites may play a role in the development of hypertension in Sabra rats.

Adrenergic alpha-Antagonists↗
PubMed1989

Efficacy and safety of cilazapril in elderly patients with essential hypertension. A multicenter study.

The efficacy and safety of cilazapril monotherapy was evaluated in a multicenter, open-label, ascending-dose titration study in 83 elderly essential hypertensive patients. After a four-week, single-blind, placebo run-in period, patients received 1 mg of cilazapril once daily for the first four weeks. This dose was then increased to 2.5 mg once daily for the next four weeks for patients whose pre-dose sitting diastolic blood pressure was above 90 mm Hg. Similarly, at Week 8 the dose was increased in such patients from 1 to 2.5 mg or from 2.5 to 5 mg once daily. A 12-hour blood pressure profile was performed on the first day of active treatment and of each dose increase. Mean decrease of sitting diastolic blood pressure from baseline (102.7 +/- 0.4 mm Hg) at Week 12 was 13.3 +/- 1.1 mm Hg (p less than 0.001). Seventy-five percent of patients had a decrease of 10 mm Hg or more from baseline sitting diastolic blood pressure, and in 60 percent sitting diastolic blood pressure normalized. Unexpectedly large decreases of blood pressure after the first dose were seen only in three patients and none had clinical symptoms. Fourteen patients (16.9 percent) reported adverse events, but most of these were judged unlikely to be related to therapy. Four patients with predisposing underlying diseases experienced potentially serious adverse events (angina pectoris, myocardial infarction, arrhythmia, and blood pressure elevation) whose relationship to therapy was judged remote or only possible. There was no particular pattern of changes in laboratory values. The results indicate that cilazapril is an effective, safe, and well-tolerated antihypertensive drug for the elderly.

Aged↗
PubMed1989

Alpha-adrenoceptor properties in rat strains sensitive or resistant to salt-induced hypertension.

Cerebral and renal alpha 2-adrenoceptors are implicated in the control of sympathetic activity and of sodium reabsorption respectively. In addition, sodium ions play an important role in the regulation of either alpha 2-adrenoceptor densities and affinities for adrenergic agonists. In the present study, alpha-adrenoceptor properties were investigated in genetically predetermined salt-sensitive and salt-resistant Dahl and Sabra rats. Cerebral alpha 2-adrenoceptor densities were higher in salt-resistant than in salt-sensitive Dahl and Sabra rats. In contrast, renal alpha 2-adrenoceptor density was higher in salt-sensitive than in salt-resistant rats. No difference in cerebral and renal alpha 1-adrenoceptor densities was observed between Dahl and Sabra substrains. Noradrenaline content in cerebral and renal cortex were also similar in both these rat substrains. Sodium ions markedly increased cerebral and renal high-affinity alpha 2-adrenoceptor densities in salt-sensitive but not in salt-resistant rats. Cerebral and renal alpha 1-adrenoceptor densities were unchanged in salt-sensitive and salt-resistant substrains of Dahl and Sabra rats. In addition, sodium ions reduced the affinity of adrenaline for renal alpha 2-adrenoceptors in salt-sensitive rats but not in salt-resistant rats. We can conclude that there exist genetically determined differences in the densities and properties of cerebral and renal alpha 2-adrenoceptors between salt-sensitive and salt-resistant rat strains. Abnormal densities of alpha 2-adrenoceptors may play a primary role in the role in the development of hypertension in salt-sensitive animals. These results also suggest an association between absence of sodium regulation of alpha 2-adrenoceptors and resistance to salt-induced hypertension. The absence of sodium regulation in salt-resistant rats may be linked either to a particular receptor conformation or to an abnormal structure of the receptor system. This property may represent a genetically-mediated change responsible for the resistance to the development of salt-induced hypertension.

Animals↗
PubMed1988

Effects of DOCA-salt treatment on the urinary prostaglandins in Sabra rats.

To determine whether the increased renal synthesis of thromboxane (Tx)A2 found in genetically hypertensive rats also occurred in rats with a sodium-dependent form of hypertension, the urinary excretion of 6-keto-prostaglandin F1 alpha (6KPGF1 alpha) and of TxB2 was measured by a sensitive and specific radioimmunoassay in hypertension-prone (SBH), -resistant (SBN) and unselected (SB) female rats of the Sabra strains. Rats of the three strains were studied before (9 weeks of age) and after five weeks of deoxycorticosterone (DOCA)-salt treatment. Before treatment, the urinary 6KPGF1 alpha did not differ among the three strains while a higher TxB2 excretion was seen in the SBN rats. After treatment, the urinary excretion of TxB2 increased significantly in SBH and SB but not in SBN rats, while the urinary 6KPGF1 alpha remained unchanged in SBH, increased moderately in SB and markedly in SBN controls. Consequently, DOCA-salt-induced changes in blood pressure and in urinary 6KPGF1 alpha observed in the three strains of rats were inversely related (r = -0.78; P less than 0.001). It is concluded that the high blood pressure developed after DOCA-salt treatment in SBH rats is more likely to depend upon a defect in the renal production of prostacyclin rather than upon an increased synthesis of thromboxane A2.

6-Ketoprostaglandin F1 alpha↗
PubMed1988

Alpha-adrenoceptors in Dahl hypertensive and normotensive rats: effect of sodium.

Sodium ions play an important role in vitro and in vivo in the regulation of alpha 2-adrenoceptors. The in vitro effect of sodium on cerebral and renal alpha-adrenoceptors was investigated in Dahl salt-sensitive and salt-resistant rats. Cerebral alpha 2-adrenoceptor densities were higher in Dahl salt-resistant rats. In contrast, the renal alpha 2-adrenoceptor density was higher in Dahl salt-sensitive than in Dahl salt-resistant rats. No difference in cerebral and renal alpha 1-adrenoceptor densities was observed between the two types of rat. Noradrenaline contents in the cerebral and renal cortex were also similar in these two rat substrains. An influx of sodium ions markedly increased cerebral and renal high-affinity alpha 2-adrenoceptor densities in Dahl salt-sensitive but not in Dahl salt-resistant rats. Under these conditions alpha 1-adrenoceptor densities remained unchanged. The absence of sodium regulation in Dahl salt-resistant rats may be linked either to a particular receptor conformation or to an abnormal structure of the alpha 2-adrenoceptor system. We conclude from the present study that there are marked differences in density and in the role of sodium regulation of cerebral and renal alpha 2-adrenoceptors from salt-sensitive and salt-resistant Dahl rats. These differences may play a primary role in the resistance or in the sensitivity of salt-induced hypertension.

Animals↗
PubMed1988

Nitrendipine prevents the development of cardiac hypertrophy in DOCA-salt-treated hypertension-prone (SBH) and -resistant (SBN) rats through nonhemodynamic mechanisms.

Recent studies indicate that cardiac and renal hypertrophy develop during desoxycorticosterone acetate (DOCA)-salt (DOC) treatment in hypertension-prone (SBH) and -resistant (SBN) rats, irrespective of systemic hemodynamic changes. The effect of nitrendipine on the development of left and right ventricular hypertrophy (LVH and RVH, respectively) was evaluated in 16-week-old rats. Members of each strain were divided into six groups (n = 10): 1--control; 2--nitrendipine treated for 3 weeks; 3, 4, and 5--DOC for 10 days, 3 weeks, and 6 weeks, respectively; 6--DOC for 6 weeks and nitrendipine for the last 3 weeks. Cannulae were inserted into the left ventricle and abdominal aorta. The radioactive reference sample microsphere technique was used to measure cardiac index. Mean arterial pressure (MAP) and total peripheral resistance index (TPRI) were unchanged in all six groups of SBN rats, whereas MAP and TPRI increased progressively in the DOC-treated SBH groups. Concomitant administration of nitrendipine in Group 6 was associated with a reduction of MAP and TPRI to control levels. Cardiac index and heart rate did not change in any group. Despite the different hemodynamic changes, both SBH and SBN rats developed LVH and RVH. The concomitant administration of nitrendipine prevented the progression of LVH and allowed regression of RVH in both strains. It is concluded that nitrendipine can affect the pathogenesis of LVH through nonhemodynamic mechanisms.

Animals↗
PubMed1988

[Hereditary resistance to salt-induced hypertension. What mechanisms?].

The Sabra hypertension resistant rats (SBN) have an outstanding ability to maintain normal blood pressure when exposed to procedures that ordinarily cause hypertension in normal rats. The following findings may be relevant to resistance to hypertension of these rats: 1) In SBN rats, cardiac norepinephrine content is not affected by DOCA-salt treatment. Since depletion of cardiac norepinephrine is an index of cardiac adrenergic nerve overactivity, the results suggest an attenuated cardiac sympathetic nerve activity in these rats. 2) In SBN rats, the sensitivity of the baroreflex control of the heart is markedly increased compared with other strains. Reduction of baro-receptor sensitivity by aortic-baroreceptor deafferentation renders them susceptible to DOCA-salt hypertension. The results suggest a strong relationship between baroreflex supersensitivity and resistance to hypertension in these rats. 3) The amount of alpha 2 adrenoreceptor densities in cerebral and renal cortical membranes of normal rats increased in vitro, in the presence of sodium and guanyl nucleotide (GTP). In SBN rats, the effect of sodium is markedly attenuated compared with SBH, while response to GTP is identical in the two strains. The demonstration of a similar pattern of response in the Dahl rats suggests that alpha 2 adrenoreceptor may be involved in the sensitivity or resistance to salt induced hypertension.

Animals↗
PubMed1987

Nifedipine corrects the blunted renal response to saline loading in hypertension-prone SBH rats.

The elimination of an acute oral saline load is markedly blunted in adult Sabra hypertension-prone (SBH) rats compared with hypertension-resistant Sabra normotensive (SBN) rats. Within 2 h, urinary output and the excretion of sodium and potassium are significantly reduced, while urine osmolality is markedly elevated in SBH rats. The long-term administration of nifedipine, 20-30 mg/kg body weight enhanced the diuretic and natriuretic response to saline loading in members of both strains. The effect was significantly more pronounced in SBH, especially in adult animals where the diuretic and natriuretic response averaged 150 and 130% of control, while in SBN the enhanced response was 50 and 20%, respectively. As a result of the disparate effect of nifedipine in the two strains, the blunted response of SBH was abolished. The mechanism of the preferential response to nifedipine of SBH rats remains to be determined.

Animals↗
PubMed1986

Calcium channel blockers in the management of hypertension in the elderly.

Calcium channel blockers seem to be particularly suitable for elderly hypertensive patients since these agents do not cause salt and fluid retention, postural hypotension, sedation, depression, or biochemical abnormalities. Moreover, their use is compatible with several common diseases of old age, such as diabetes, obstructive lung disease, and peripheral vascular disease. We recently conducted a study in 21 patients (average age, 79 +/- 2 years) who completed an eight-week trial with 20-mg nifedipine tablets taken twice daily. Mean blood pressure decreased from 191 +/- 2/96 +/- 2 mm Hg to 151 +/- 4/80 +/- 3 mm Hg. In 15 patients (71 percent), blood pressure decreased to less than or equal to 160/90 mm Hg; in four additional patients (19 percent), diastolic blood pressure decreased by 15 to 25 percent. Thus, there was a sustained lowering of blood pressure in 90 percent of the participants receiving nifedipine monotherapy. A review of recent studies in elderly hypertensive patients revealed similarly favorable results with calcium channel blockers given alone or in combination with other agents. The accumulating data suggest that these compounds may offer a useful new approach to the treatment of hypertension in old age. However, in these studies, the number of patients and the duration of follow-up need to be extended to confirm the favorable impression obtained thus far.

Aged↗
PubMed1986

Changes in central alpha-adrenoceptors and noradrenaline content after high sodium intake in Sabra salt-sensitive and salt-resistant rats.

Several studies have suggested a correlation between sodium accumulation and the development of hypertension. However, the mechanisms whereby sodium is able to increase blood pressure remain unclear. In the present study, alpha-adrenoceptors and noradrenaline contents have been studied in the cerebral cortex, hypothalamus and medulla oblongata in the Sabra rat strain in order to define their role in the resistance or sensitivity to sodium-induced hypertension. Alpha-Adrenoceptors were defined using the selective ligands 3H-prazosin and 3H-rauwolscine for alpha 1- and alpha 2-adrenoceptors, respectively. Under normal sodium diet, alpha 2-adrenoceptor density was higher in cerebral cortex and lower in hypothalamus and medulla oblongata of SBN (salt-resistant) compared to SBH (salt-sensitive) rats. Five weeks of high sodium intake induced a decrease in alpha 2-adrenoceptor density in cerebral cortex and an increase in hypothalamus only in SBN rats. These changes abolished the differences between SBH and SBN rats observed with a normal sodium diet. No changes in density and affinity of alpha 2-adrenoceptors were observed in medulla oblongata of SBN and SBH rats. Density and affinity of alpha 1-adrenoceptors were similar in SBN and SBH rats in all the tissues studied and they were unaffected by the high sodium diet. Noradrenaline contents in cerebral cortex, hypothalamus and medulla oblongata were also similar in the two rat substrains under normal sodium diet, but high sodium intake induced a decrease cerebrocortical noradrenaline content only in SBN rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Sodium handling by the Sabra hypertension prone (SBH) and resistant (SBN) rats.

The acute and chronic renal handling of salt was evaluated in age matched Sabra hypertension-prone (SBH) and hypertension-resistant (SBN) rats. Acute oral (4 ml/100 g) and intravenous (3.3 ml/100 g) isotonic saline loading in unanesthetized normotensive animals maintained on normal diet elicited a significantly lesser diuretic and natriuretic response in SBH than in SBN. Intermittent studies in metabolic cages in rats aged 5 to 21 weeks showed that both strains consumed similar amounts of salt but that SBH excreted significantly less urinary sodium than SBN (F = 40, p less than 0.001). Twenty four hour clearance studies showed a similar filtered sodium load in the two strains but a lower total and fractional sodium excretion in SBH, suggesting increased tubular reabsorption. Under conditions of water diuresis, free water clearance was similar in the two strains, suggesting the site for disparate tubular sodium handling to be distal to the thick medullary ascending limb of the loop of Henle. Acute oral saline loading and long term studies in metabolic cages in rats prepared with deoxycorticosterone-acetate (doca) and salt showed no significant differences in sodium excretion between hypertensive SBH and normotensive SBN. These findings indicate disparate renal sodium handling between SBH and SBN rats, already apparent before the onset of hypertension, which dissipates during doca-salt treatment.

Age Factors↗
PubMed1986

Comparison of various genetic hypertensive rat strains.

Comparative studies on nine genetic hypertensive rat strains [two stroke-prone spontaneously hypertensive rats (SHRSP) and Dahl salt-sensitive (DS) strains, and one strain each of spontaneously hypertensive rats (SHR), Lyon hypertensive rats (LH), Milan hypertensive strain (MHS), genetically hypertensive rats (GH) and Sabra hypertensive rats (SBH)] and their respective controls [two Dahl salt-resistent (DR) strains and one strain each of Wistar-Kyoto rats (WKY), Lyon normotensive rats (LN); Lyon low blood pressure rats (LL), Milan normotensive strain (MNS), genetically normotensive rats (GN) and Sabra normotensive rats (SBN) and their original strain, Sabra rats (SB)], in groups consisting of 6-10 males from each strain, were carried out at 10-12 weeks of age under the same experimental conditions. After checking the developmental course of blood pressure and changes in body weight, they were killed at 12 weeks of age for blood analysis and organ-weight examinations. The SHRSP and SHR showed markedly higher blood pressure levels and earlier blood pressure rises in comparison with other hypertensive strains, although they had higher blood pressure than their respective controls. Among various organ weights examined, all hypertensive strains commonly showed increases in left ventricular weight in proportion to blood pressure rises. Kidney weights were significantly decreased only in MHS compared with MNS, while they were either unchanged or significantly greater in other hypertensive strains. Weights of adrenal glands were greater in the two strains of DS and in LH than in their respective control strains. These comparative data indicate possible differences in the pathogenic mechanism involved in these genetic hypertensive rat strains.

Animals↗
PubMed1985

Sabra rats as a model to differentiate between Na+ and GTP regulation of alpha 2-adrenoceptor densities.

Sodium ions and guanyl nucleotides play an important role in increasing alpha 2-adrenoceptor densities in cerebral and renal cortex of normotensive rats. The in vitro effect of Na+ and GTP was investigated on cerebral and renal alpha-adrenoceptors in hypertensive (SBH, salt-sensitive) and normotensive (SBN, salt-resistant) Sabra rats. In SBH and SBN rats, guanyl nucleotides increased cerebral and renal high-affinity alpha 2-adrenoceptor densities. Sodium ions, in contrast, markedly increased cerebral and renal high affinity alpha 2-adrenoceptor densities only in SBH rats. Under these conditions, alpha 1-adrenoceptor densities were unchanged. Thus, although Na+ and GTP both increase alpha 2-adrenoceptor densities, these agents appear to mediate their regulatory effects via different membrane components. Moreover, the absence of sodium regulation of alpha 2-adrenoceptors in SBN rats may be responsible for the resistance to salt-induced hypertension.

Animals↗