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PubMed1988

Glomerular and vascular atrial natriuretic factor receptors in saralasin-sensitive and -resistant two-kidney, one-clip hypertensive rats.

We have investigated whether there is a relation between renin dependency of two-kidney, one-clip (2K1C) hypertensive rats and the density of renal glomerular and vascular atrial natriuretic factor (ANF) receptors. Conscious 2K1C rats with blood pressure of 150 mm Hg or higher were classified according to their sensitivity to the blood pressure-lowering effect of the angiotensin II antagonist saralasin. Both hypertension groups had lower body weights and greater relative heart weights than normotensive controls. Hematocrit was lower and plasma volume higher in saralasin-resistant animals than in either saralasin-sensitive or control rats. Plasma renin activity was higher in the saralasin-sensitive group than in the resistant rats. Plasma ANF concentration was greater in saralasin-resistant than in either normotensive or saralasin-sensitive animals. ANF was reduced in both atria of saralasin-resistant 2K1C animals but only in the left atrium of the sensitive group. Both hypertensive groups showed an increased ventricular ANF concentration. The number of glomerular ANF binding sites was significantly lower in the clipped kidney of both hypertensive groups. This lower density of binding sites was accompanied by an increased affinity. In saralasin-sensitive rats, the density of glomerular ANF receptors in the nonclipped kidney was significantly higher than in the controls. Saralasin-resistant rats exhibited a decreased number of vascular ANF binding sites in both mesenteric arteries and aorta. We conclude that through modulation of its glomerular and vascular receptors, ANF may contribute to the differential sodium handling of saralasin-sensitive and -resistant 2K1C hypertensive rats and to the reduced vascular responsiveness to ANF observed in the saralasin-resistant hypertensive rats.

Animals↗
PubMed1978

Pharmacokinetic and pharmacodynamic studies of infusions with [Sar 1, Val5, Ala8] angiotensin II (saralasin).

A modification of the infusion test with saralasin, an angiotensin II antagonist for the detection of renin-dependent high blood pressure was studied in renal hypertensive rats and in normotensive and hypertensive subjects. Infusion was started at a rate of 0.01 microgram/kg x min saralasin and the dose was increased ten-fold at 15 min intervals. A significant fall of diastolic blood pressure was observed at the dose of 0.1 microgram/kg x min in renal hypertensive rats, in healthy subjects treated with diuretics, and in patients with renovascular hypertension (saralasin responders). Plasma concentrations of angiotensin I, angiotensin II and of saralasin as well as plasma renin activity were measured. At the lowest infusion rate of 0.01 microgram/kg x min, saralasin plasma levels were 40-fold higher than plasma angiotensin II levels. The decrease in arterial blood pressure occurred at lower doses of saralasin than the increase of plasma renin due to inhibition of feedback on the renin secreting cells. It is concluded that if the saralasin test is performed by a stepwise increase of the infusion rate, potentially dangerous complications such as hypo- or hypertensive reactions can be avoided. The diagnostic reliability is improved by such a procedure since false positive and false negative responses may be prevented. The pressor effect of saralasin in non-renin dependent patients is an advantage since it causes a more marked difference of blood pressure change between saralasin responders and non-responders.

Angiotensin I↗
PubMed1983

Slow rise and diurnal change of blood pressure with saralasin and angiotensin II in rats.

Our objectives were to determine whether saralasin, like angiotensin II, raises blood pressure gradually when given by constant infusion and whether either agent alters the diurnal variation of arterial pressure. Eight female Wistar rats were infused intravenously with 5% dextrose for 2 days, then with saralasin at 10 micrograms . kg-1 . min-1 for 4 days, and finally with dextrose for 2 days. Six other rats were infused with angiotensin II (20 ng . kg-1 . min-1) instead of saralasin. Mean arterial pressure (MAP) was recorded continuously. Saralasin and angiotensin II gradually raised MAP in all rats, by 22.0 mmHg on the 4th day of saralasin and by 41.7 mmHg on the 4th day of angiotensin II. Both agents also increased the diurnal variation of blood pressure, MAP increasing 8.3-20.6 mmHg during the night and falling 6.7-19.1 mmHg during the day. Variability of arterial pressure was also increased by saralasin and in an earlier experiment by angiotensin II. We conclude that saralasin has a slow pressor action similar to that of angiotensin II but distinct in its timing both from the rapid agonist action of saralasin and from the acute vasoconstrictor action of angiotensin II. These effects of saralasin may compromise interpretation of experiments in which the drug is given by prolonged infusion to assess the role of angiotensin II.

Angiotensin II↗
PubMedDate not supplied

Saralasin-induced renin release: its blockade by prostaglandin synthesis inhibitors in the conscious rat.

The angiotensin antagonist, saralasin, (10 and 30 mg/kg), increased serum renin activity (SRA) in normal, conscious rats from 2.7 +/- 0.4 to 16.2 +/- 3.7 and 22.5 +/- 2.4 ng/ml/hr (p less than 0.001), respectively, without markedly altering blood pressure or heart rate. Indomethacin, in a dose which inhibited the urinary excretion of prostaglandin E2 (PGE2) by 75%, and arachidonate-induced hypotension by 83%, failed to alter basal SRA but inhibited saralasin-induced renin release by 99% and 87% at the 10 and 30 mg/kg doses, respectively. Indomethacin failed to alter basal hemodynamics or the hemodynamic response to saralasin. Propranolol (1.5 mg/kg) inhibited saralasin-induced renin release by 93% and enhanced the suppressant effect of indomethacin from 79% to 100%. Meclofenamate, another prostaglandin synthesis inhibitor, also blocked saralasin-induced renin release by 99% and 72% at the 10 and 30 mg/kg doses, respectively (p less than 0.001). In sodium-depleted rats, saralasin (0.3 mg/kg) increased SRA from 12 +/- 2 to 119 +/- 6 ng/ml/hr (p less than 0.001) and decreased blood pressure by 6% (p less than 0.01). In these animals, indomethacin failed to alter basal SRA, but inhibited saralasin-induced renin release by 82%, urinary excretion of PGE2 by 79%, and arachidonate-induced hypotension by 81%. These findings suggest 1) that saralasin-induced renin release is mediated by renal prostaglandins, and 2) an interrelationship exists between the receptor controlling AII-mediated inhibition of renin release, which is blocked by saralasin, and the juxtaglomerular beta-adrenergic receptor.

Animals↗
PubMed1977

Pressor response to 1-sar-8-ala-angiotensin II (saralasin) in hypertensive subjects.

An angiotensin II (A II) analogue (1-Sar-8-Ala-angiotensin II) (saralasin) was infused into 418 untreated hypertensive subjects during a 1-day evaluation while blood pressure was recorded every 2 minutes by Arteriosonade. At 5 mug/kg per min, saralasin produced a change in mean blood pressure which correlated significantly (r=-0.54, P less than 0.001) with the stimulated plasma renin activity (PRA) (after intravenous furosemide and ambulation for 2 hours. Saralasin caused a rise inmean blood pressure of at least 7.0 mm Hg in 97 hypertensive subjects, who also had a low stimulated PRA (1.3+/-SEM, 0.1 ng/ml per hour; normal range, 1.7-8.5). On a low sodium diet, the pressor response of hypertensive subjects to saralasin continued and was an even better indicator of a low stimulated PRA. Infusion of saralasin at 10 mug/kg per min into normal subjects on an unrestricted diet, a low sodium diet, and a high sodium diet produced, respectively, no change, a fall (P less than 0.05), and a rise (P less than 0.005) in blood pressure. The same saralasin dose in six hypertensive subjects who showed a pressor response to the analogue in the 1-day study also produced a rise in blood pressure when given on a low sodium diet, and this rise was more than twice that seen in normal subjects on a high sodium diet. Hypertensive subjects who showed the pressor response had a significantly greater (P less than 0.01) pressor sensitivity to A II than did hypertensive nonresponders to saralasin and noraml subjects on an uncontrolled diet. The affinity of the vascular receptors for the analogue was greater in the hypertensive group that showed the pressor response to saralasin. In summary, the pressor response to saralasin, as defined above, occurred in 23% of a large unselected group of hypertensive subjects and was associated with salt loading, a low stimulated PRA, and increased pressor sensitivity to A II.

Adult↗
PubMed1978

Effect of saralasin upon plasma catecholamines in hypertensive patients.

The effect of saralasin, a clinically employed angiotensin antagonist, upon hemodynamics and plasma catecholamine concentration was compared to the infusion of noradrenaline. These studies were carried out to determine if a transient pressor effect frequently observed during saralasin infusion might be mediated by release of catecholamines from the adrenal medulla. After five minutes of saralasin infusion, mean arterial pressure rose significantly, pulse rate fell slightly, and plasma noradrenaline increased by 115 +/- 28 pg./ml. Plasma adrenaline was unchanged. After 30 minutes of saralasin infusion, mean arterial pressure was at control levels and plasma catecholamine concentrations were also no different from pre-infusion levels. Infusion of noradrenaline produced a hemodynamic pattern similar to that observed during the first five minutes of saralasin infusion. However, there was a thirteen-fold increase of plasma noradrenaline observed when compared to the first five minutes of saralasin infusion. It was concluded that the transient pressor action of saralasin could not be explained by release of catecholamines from the adrenal medulla. However, the very slight increase in plasma norepinephrine observed during the first five minutes of saralasin infusion may imply altered function of sympathetic neurons.

Angiotensin II↗
PubMed1984

Differential prejunctional effect of captopril and saralasin on neurogenic vasoconstriction in pithed normotensive rats.

The present study describes a differential inhibitory effect of captopril and [Sar1 Ala8]angiotensin II (saralasin) on the neurogenic vasoconstriction in pithed normotensive rats. In pithed normotensive rats with intact kidneys captopril more profoundly inhibited the vasopressor response to spinal stimulation than observed for saralasin. Bilateral nephrectomy also diminished the hypertensive response to spinal stimulation. After bilateral nephrectomy, 1 h previously, captopril but not saralasin diminished the hypertensive response to spinal stimulation. After bilateral nephrectomy, 18-24 h previously, captopril did not produce an additional reduction of the vasopressor response to spinal stimulation. In contrast, saralasin significantly potentiated the neurogenic vasoconstriction. The results suggest that both captopril and saralasin diminish the hypertensive response to spinal stimulation by producing dilatation of vascular smooth muscle in pithed normotensive rats. Apart from this common mechanism, a differential effect of captopril and saralasin on the neurogenic vasoconstriction can be observed. In contrast to saralasin, captopril may depress the neurogenic vasoconstriction in pithed normotensive rats by blocking the sympathofacilitatory action induced by subpressor levels of angiotensin II (AII). In pithed normotensive rats, saralasin may mimic the sympathofacilitatory action of subpressor AII.

Animals↗
PubMed1980

Saralasin test as a diagnostic and prognostic aid in renovascular hypertensive patients subjected to renal operation.

A positive saralasin test in patients with angiographic evidence of renovascular disease and other positive functional tests gives further assurance that these patients will achieve normal or substantially reduced blood pressure postoperatively. In our experience with proved renovascular hypertension there was a 19 per cent incidence of falsely negative saralasin tests. Therefore, saralasin should not be used as the sole screening test in hypertensive patients suspected of having surgically correctable lesions. There is a direct correlation between elevated renin activity and a positive saralasin test. In some patients saralasin may be more sensitive than any other currently used test to detect overactivity of the renin-angiotensin system. This would determine those patients with technical errors in renin sampling and assays. Of the 16 patients (all normotensive) who had 6-month followup tests 5 had elevated peripheral renin activity, probably owing to furosemide stimulation. Of these 5 patients 2 had a positive postoperative saralasin test, raising the question of potential falsely positive responses in cases of essential hypertension and coincidental non-functional renal artery stenosis. Patients with high renin essential hypertension may respond to saralasin, even in the absence of renal artery lesions. A saralasin test should be done in a hospital where all specific conditions can be met and potential complications handled promptly.

Adolescent↗
PubMed1979

Saralasin test as a diagnostic and prognostic aid in renovascular hypertensive patients subjected to renal operation.

A positive saralasin test in patients with angiographic evidence of renovascular disease and other positive functional tests gives further assurance that these patients will achieve normal or substantially reduced blood pressure postoperatively. In our experience with proved renovascular hypertension there was a 19% incidence of falsely negative saralasin tests. Therefore, saralasin should not be used as the sole screening test in hypertensive patients suspected of having surgically correctable lesions. There is a direct correlation between elevated renin activity and a positive saralasin test. In some patients saralasin may be more sensitive than any other currently used test to detect overactivity of the renin-angiotensin system. This would determine those patients with technical errors in renin sampling and assays. Of the 16 patients (all normotensive) who had 6-month followup tests 5 had elevated peripheral renin activity, probably owing to furosemide stimulation. Of these 5 patients 2 had a positive postoperative saralasin test, raising the question of potential falsely positive responses in cases of essential hypertension and coincidental non-functional renal artery stenosis. Patients with high renin essential hypertension may respond to saralasin, even in the absence of renal artery lesions. A saralasin test should be done in a hospital where all specific conditions can be met and potential complications handled promptly.

Adult↗
PubMedDate not supplied

Systemic hemodynamic and hormonal responses during angiotensin II blockade with saralasin.

The effect of saralasin infusion on systemic hemodynamics, plasma renin activity (PRA), and aldosterone levels was studied under various conditions of sodium balance in 25 patients with essential hypertension. The results of 66 paired observations were statistically analyzed, to elucidate some controversial aspects of the mechanisms of saralasin action. The total peripheral resistance index (TPRI) increased when saralasin had an agonistic effect on blood pressure (BP) and decreased when it acted as an antagonist. The TPRI changed more than the BP by an inversely directed change in the cardiac index (CI). In addition, the changes in the CI were only weakly correlated with the changes in MAP; CI decreased consistently when BP increased but showed no distinct pattern when saralasin acted as an antagonist. The pulse rate did not change under any of the conditions applied. The present findings suggest that in addition to its antagonistic effects on peripheral circulation, saralasin has some action on the heart and autonomic nervous system. The observed changes in the plasma aldosterone level were in accordance with the changes in TPRI and did not point to a difference between adrenal and vascular sensitivity to saralasin or angiotensin II. The overall hemodynamic responses were related to the existing level of PRA. No correlation was found between the degree of volume depletion and the blood pressure response during saralasin after elimination of the effect of PRA by partial regression analysis. These findings do not support the concept that more information about the renin dependency of the BP is provided by the BP reaction to saralasin than by determination of the PRA.

Aldosterone↗
PubMed1978

The effect of an angiotensin antagonist (saralasin) on arterial pressure and plasma aldosterone in hemodialysis-resistant hypertensive patients.

The effect of an angiotensin II antagonist (saralasin) on arterial pressure, plasma renin activity (PRA) and plasma aldosterone concentration (PAC) was assessed in seven dialysis-resistant hypertensive patients. During saralasin infusion performed before hemodialysis, mean arterial pressure fell by 8 to 18.3% in six out of the seven subjects; arterial pressure was normalized in three of them. After hemodialysis (6 subjects), a normal arterial pressure was achieved in five patients. One patient was resistant to saralasin before and after dialysis. A negative correlation (r = 0.62) was obtained between pre-infusion PRA and the change in mean arterial pressure induced by saralasin. Post-infusion PRA increased in saralasin responsive patients, the change in PRA being correlated (r = 0.82) with the pre-infusion PRA. Plasma aldosterone concentration was variably affected by saralasin; a negative correlation between pre-infusion PAC and the absolute change in PAC during saralasin was obtained (r = 0.72). The role of angiotensin II in the maintenance of a high arterial pressure in chronic dialysis patients was demonstrated. In saralasin-resistant patients, more vigorous ultrafiltration is proposed.

Adult↗
PubMedDate not supplied

Graded effects of saralasin on prostaglandin E, plasma renin activity and renal blood flow in anaesthetized dogs.

The objective of this study was to examine in anaesthetized dogs the graded effect of saralasin on renal prostaglandin E (PGE) release and to attempt to associate this change with its effects on plasma renin activity and renal blood flow. Blood pressure and renal blood flow were monitored. Renal PGE concentration and plasma renin activity were measured by radioimmunoassay. Saralasin or saline vehicle was infused into the renal artery for 20 min. Infusion of saralasin at the lowest dose of 0.25 micrograms/kg per min or saline vehicle did not alter either renal blood flow or plasma renin activity. Saralasin increased renal blood flow and caused a complete blockade of the renal vasoconstrictor response to exogenous angiotensin II at the two higher doses used (0.5 and 1 micrograms/kg per min). Only the highest dose of saralasin increased plasma renin activity significantly. Renal venous PGE concentration at the 5, 10 and 20 min periods of infusion was not changed significantly by any of these three doses of saralasin. We conclude therefore that the increases in renal blood flow and plasma renin activity caused by saralasin in the anaesthetized dog occur by mechanisms independent of changes in renal PGE.

Animals↗
PubMedDate not supplied

Saralasin dilates arterioles in SHR but not WKY rats.

Microvascular responses to topical or intravascular saralasin were determined in the cremaster muscle arterioles of adult spontaneously hypertensive rats (SHR, n = 19) and Wistar-Kyoto (WKY, n = 16) normotensive rats. Animals were anesthetized with chloralose and urethane, and they breathed room air spontaneously. Mean arterial pressure was obtained from a catheter in a carotid artery, and microvascular diameters were determined by video microscopy. Plasma renin activity was measured in animals that were treated identically except that saralasin was not administered. For all animals, mean arterial pressure averaged 126 +/- 4 mm Hg in SHR and 82 +/- 4 mm Hg (p less than 0.001) in WKY rats. Topical saralasin, 10(-6)M, was applied to the cremaster muscles of SHR (n = 9) or WKY (n = 8) rats while internal diameters of first-through fourth-order arterioles (A1, A2, A3, A4) were measured. Topical saralasin did not alter arteriolar diameters (A1 through A4) in WKY rats, but A3 and A4 vessels dilated significantly (29% +/- 5% and 38% +/- 7% respectively; p less than 0.01) in SHR. Fourth-order diameters were measured in other SHR (n = 10) and WKY (n = 8) rats while saralasin was administered intraarterially (300 micrograms bolus into the hypogastric artery) or intravenously (10 micrograms/kg/min for 30 minutes). Intraarterial or intravenous saralasin caused significant dilation (32% +/- 12% and 20% +/- 4%, respectively; p less than 0.01) of A4 arterioles in SHR, but no dilation occurred in the arterioles of WKY rats. Arteriolar responses were significantly different (p less than 0.001) in SHR vs WKY rats for both the topical and the intravascular administration of saralasin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1979

Glomerular hemodynamics in rats with chronic sodium depletion. Effect of saralasin.

In chronic sodium depletion the glomerular filtration rate may be reduced, and alterations in proximal tubular function may contribute to the maintenance of antinatriuresis. Measurements were made by micropuncture technique in superficial nephrons of the Munich-Wistar rat of (a) the determinants of glomerular filtration rate, (b) peritubular capillary hydrostatic and oncotic pressure, and (c) proximal tubular fractional and absolute reabsorption in both a control group (group 1, n = 12) and a group of chronically sodium-depleted rats (group 2, n = 12). Single nephron filtration rate (sngfr) was 37.2+/-1.2 in group 1 and 31.6+/-1.0 nl/min/g kidney wt (P < 0.05) in group 2. Of the factors potentially responsible for the observed reduction in sngfr, there was no change in systemic oncotic pressure or the transglomerular hydrostatic pressure gradient. Sngfr was lower in group 2 because of both a reduced single nephron plasma flow (rpf) (128+/-6 vs. 112+/-5 nl/min per g kidney wt, P < 0.05) and additionally to a decrease in the glomerular permeability coefficient, L(p)A, from a minimum value of 0.105+/-0.012 in group 1 to 0.054+/-0.01 nl/s per g kidney wt per mm Hg (P < 0.01) after chronic sodium depletion. There was no difference in fractional proximal tubular reabsorption between group 1 and group 2. Absolute proximal reabsorption (APR) was reduced from 20.8+/-1.3 in group 1 to 16.3+/-0.9 nl/min per g kidney wt in group 2. The role of angiotensin II (AII) in maintaining glomerular and proximal tubular adaptations to chronic sodium depletion was assessed in subsets of groups 1 and 2 by the infusion of the AII antagonist Saralasin at a rate of 1 mug/kg per min. In group 1 rats, Saralasin had no effect on sngfr, rpf, or L(p)A, because animals remained at filtration pressure equilibrium. In group 2 rats, AII blockade was associated with an increase in sngfr from 31.6+/-1.0 to 37.1+/-1.7 nl/min per g kidney wt (P < 0.01). Rpf increased during Saralasin infusion solely as a result of a decrease in afferent arteriolar resistance from 21.7+/-2.3 to 15.2+/-2.3 10(9) dyn-s-cm(-5) (P < 0.01). Saralasin infusion did not affect the reduced L(p)A in group 2, as L(p)A remained 0.056+/-0.02 nl/s per g kidney wt per mm Hg and rats remained disequilibrated. In spite of the increase in sngfr in group 2, AII antagonism further decreased APR to 13.1+/-1.5 (P < 0.01). Distal delivery therefore, increased from a control value of 15.3+/-1.3 to 24.3+/-1.5 nl/min per g kidney wt (P < 0.01). In conclusion, both a decrease in L(p)A and a reduction in rpf were major factors mediating the decrease in glomerular filtration rate observed in chronic sodium depletion. Saralasin infusion revealed a significant effect of AII on rpf and afferent arteriolar resistance in chronic sodium depletion, but no effect of AII on either efferent arteriolar resistance or the decrease in L(p)A could be demonstrated. Saralasin had no effect in rats that were not chronically sodium depleted. In group 2 rats AII antagonism reduced APR even though sngfr increased, suggesting an influence of AII on proximal reabsorption. The marked changes observed during Saralasin infusion in the chronically sodium-depleted rat reveal important modifying effects of endogenously generated AII on both the glomerulus and proximal tubule.

Angiotensin II↗
PubMed1979

The effect of angiotensin II and saralasin on 18-hydroxy-11-deoxycorticosterone production by isolated human adrenal glomerulosa cells.

To assess the role of angiotensin II (AII) in regulating 18-hydroxy-11-deoxycorticosterone (18-OHDOC) secretion in man, isolated human adrenal glomerulosa cells were incubated with AII and/or its competitive antagonist, saralasin. AII 2.4 X 10(-8) M) elicited an 80% increase in 18-OHDOC levels as well as similar increases in aldosterone, 18-hydroxycorticosterone, and corticosterone (P less than 0.01). Saralasin (10(-8) M) caused a partial but significant inhibition of AII-stimulated 18-OHDOC production, while 10(-6) M saralasin blocked AII-stimulated steroidogenesis completely. In addition, both concentrations of saralasin caused 10--30% decrements in basal steroid levels. The direct AII effect on 18-OHDOC secretion and the antagonistic effect of saralasin on both exogenous and endogenous AII-stimulated steroidogenesis, documented in these experiments, indicate that the increase in 18-OHDOC levels after sodium restriction reported in man is probably mediated by the renin-angiotensin system. Furthermore, because high concentrations of saralasin did not increase aldosterone secretion, the partial agonist properties of saralasin in vivo in man may not be due to a direct effect on the glomerulosa cell.

18-Hydroxycorticosterone↗
PubMed1980

The use of an angiotensin II antagonist (saralasin) as an adjunct during renal vein catheterization.

Renal vein catheterization was performed in fifteen hypertensive patients with unilateral renal disease. Samples for measurement of plasma renin concentration were obtained from each of the two renal veins and from the femoral artery (or the inferior caval vein)-before and during saralasin infusion. Saralasin infusion induced a significant decrease in blood pressure. In ten patients with lateralization of renin secretion before infusion, saralasin induced a 2-fold increase of the renin gradient across the diseased kidney, whereas there was no significant renin gradient across the contralateral kidney neither before nor after saralasin infusion. Thus, the renal venous renin ratio (diseased/contralateral) increased from a mean value of 2.10 to 4.13. In five patients without lateralization of renin secretion prior to infusion, saralasin induced a significant increase of renin gradient across both kidneys. In consequence, evidence for lateralization did not emerge and the renal vein renin ratio remained unchanged at 1.10. In cases with lateralization of renin secretion, the use of saralasin provides confirmatory evidence for strictly unilateral renin secretion with suppression of renin output from the contralateral kidney. In patients without obvious lateralization of renin secretion before saralasin, the administration of this angiotensin II inhibitor can serve to demonstrate a potential renin for renin secretion, shared by both kidneys.

Angiotensin II↗
PubMed1997

Effects of angiotensin converting enzyme inhibitor cilazapril and angiotensin II antagonist saralasin in ovarian hyperstimulation syndrome in the rabbit.

We investigated the possible effects of the angiotensin converting enzyme (ACE) inhibitor cilazapril and angiotensin II antagonist saralasin on ovulation, ovarian steroidogenesis and ascites formation in the ovarian hyperstimulation syndrome (OHSS) in the rabbit model. OHSS was induced in rabbits by human menopausal gonadotropin (hMG) and intermittent human chorionic gonadotropin (hCG). In the cilazapril group (n = 10), animals also received cilazapril 2 mg/kg intraperitoneally daily for 7 days. In the saralasin group (n = 8), animals received saralasin intraperitoneally 1 h before or 1 h after hCG administration. Control animals (n = 8), received intraperitoneal saline solution. Serial blood samples were drawn on days 1, 5, 7 and 9 to measure serum estradiol and progesterone levels. On day 9, all rabbits underwent surgical exploration. Peritoneal and pleural fluid formation, ovarian weights and number of ovulations were determined. The volume of the ascitic and pleural fluids after hyperstimulation were not statistically different between the control, cilazapril and saralasin groups. The weight gains and ovarian weights of animals were similar between treatment and control groups. Saralasin significantly (p < 0.05) inhibited ovulation, but cilazapril did not. Cilazapril and saralasin did not affect progesterone production. Only cilazapril significantly decreased estradiol production (p < 0.05). In conclusion, the ACE inhibitor cilazapril and angiotensin II antagonist saralasin did not prevent ascites formation in OHSS. The ovarian renin-angiotensin system may not be the only factor acting in ascites formation in the OHSS.

Angiotensin II↗
PubMed1995

Saralasin suppresses arrhythmias in an isolated guinea pig ventricular free wall model of simulated ischemia and reperfusion.

The effects of saralasin on electrophysiological changes and arrhythmias induced by simulated ischemia and reperfusion were examined in an isolated tissue model. Segments of guinea pig right ventricles, stimulated regularly, were exposed to simulated ischemia for 15 min and then were reperfused with normal Tyrode's solution for 30 min. Transmembrane electrical activity and a high-gain electrogram were recorded. Arrhythmias and electrophysiological changes accompanying simulated ischemia and reperfusion in control preparations were compared to those in preparations treated with 0.1 or 1 microM saralasin. Simulated ischemia caused abbreviation of action potential duration measured at 90% repolarization, abbreviation of endocardial effective refractory period (ERP) and prolongation of transmural conduction time. Premature ventricular beats, ventricular tachycardia and conduction block were observed in approximately 35% of control preparations during simulated ischemia. Rapid sustained or nonsustained ventricular tachycardia occurred in approximately 60% of control preparations in early reperfusion. The overall incidence of arrhythmias and the incidence of ventricular tachycardia in early reperfusion were significantly decreased by 1 microM but not 0.1 microM saralasin. Saralasin (1 microM) prolonged the ERP in normoxic tissues, but it did not alter changes induced by ischemia or reperfusion in ERP or the action potential duration at 90% repolarization. Prolongation of transmural conduction time during ischemia and early reperfusion was significantly inhibited by both concentrations of saralasin. However, only 1 microM saralasin reduced the ratio of transmural conduction time to ERP enough to prevent arrhythmias. Our observations demonstrate that saralasin exerts antiarrhythmic effects in myocardial reperfusion by a mechanism independent of circulatory and central actions.

Action Potentials↗