saralasin and Body-Weight

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.

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Ascitic Fluid; Body Weight; Chorionic Gonadotropin; Cilazapril; Estradiol; Female; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation; Progesterone; Rabbits; Saralasin

One of the characteristics of early diabetic nephropathy is glomerular hyperfiltration and hyperperfusion. Many factors have been suggested to induce glomerular hyperperfusion among which are an increased production of vasodilatory prostanoids, an increased synthesis of nitric oxide, a reduced responsiveness of afferent glomerular arterioles to vasoconstrictor stimuli due to diabetic metabolic disturbances and a decreased receptor density for angiotensin II. It has been known for years that angiotensin II is formed locally due to the local activation of the renin angiotensin system. The local angiotensin II concentration, however, is not only regulated by the synthesis rate but also by the local degradation through activation of an aminopeptidase. The main finding of the present study was that the mRNA expression and activity of the angiotensin II degrading enzyme, angiotensinase A, was increased twofold in diabetic rats at 5 weeks and that the increase in mRNA expression was suppressed by insulin therapy and short-term treatment with the angiotensin II antagonist saralasin, whereas angiotensinase A enzyme activity was only reduced by saralasin and not by insulin. These results demonstrate that the angiotensin II degrading exopeptidase angiotensinase A is activated in diabetic glomeruli. This increased activity may be an additional mechanism to explain glomerular hyperfiltration and hyperperfusion in early diabetic nephropathy.

Topics: Albuminuria; Aminopeptidases; Angiotensin II; Animals; Blood Glucose; Blotting, Northern; Body Weight; Diabetes Mellitus, Experimental; Gene Expression; Glomerular Filtration Rate; Glutamyl Aminopeptidase; Immunohistochemistry; In Vitro Techniques; Insulin; Kidney; Kidney Glomerulus; Kinetics; Male; Organ Size; Rats; Rats, Wistar; Saralasin; Time Factors

Xeric-adaptation was studied during 28 days of total water deprivation (TWD) in Notomys alexis. Beyond 7 days, the initial reductions in body weight and increases in haematocrit, plasma renin and juxtaglomerular (JG) cell morphological activity returned to normal. Mus musculus showed similar changes at 7 days but could not be maintained thereafter. TWD decreased the blood pressure of Notomys but endogenous angiotensin and vasopressin did not support pressure to a greater extent than controls, as revealed by selective antagonists. The normal morphology of the JG apparatus in Notomys was similar to other rodents. Fluid volume and blood pressure maintenance during TWD in Notomys do not depend upon enhanced activities of the renin-angiotensin and antidiuretic hormonal systems.

Topics: Adaptation, Physiological; Animals; Arginine Vasopressin; Blood Pressure; Body Weight; Enalaprilat; Hematocrit; Juxtaglomerular Apparatus; Male; Mice; Mice, Inbred BALB C; Renin; Rodentia; Saralasin; Vasopressins; Water Deprivation

The serial changes in systemic and renal hemodynamics, water and electrolyte balances and various vasoactive hormones were examined in 12 conscious dogs before, during (10 days) the administration of dexamethasone (DEX: 0.5 mg/kg/day) and after the cessation of DEX. In addition, during the administration of DEX, pressor responses to angiotensin II, norepinephrine, an angiotensin II analogue, saralasin, and an alpha-1-blocker, prazosin, were studied. Abrupt elevation of blood pressure to 106 +/- 5 mmHg on Day 1 (vs. 91 +/- 6 mmHg control: P less than 0.05) associated with marked increases in total peripheral resistance (P less than 0.01) was shown in DEX treated animals. Accompanied with these changes, renal blood flow increased to 146 +/- 12 ml/min (vs. 103 +/- 8 ml/min control: P less than 0.05) on Day 1 and maintained. In contrast, the results of serial alterations in hormones could not show any significant changes except significant elevations in atrial natriuretic peptide and reductions of cortisol and arginine vasopressin. Also, marked natriuresis and diuresis were observed in DEX administration dogs. Pressor response to norepinephrine was significantly increased and administration of either saralasin and prazosin significantly reduced the blood pressure of DEX treated animals. These results in DEX-treated conscious dogs confirmed our previous findings in human and rats. Glucocorticoid-induced hypertension mainly depends on the increases in total peripheral resistance but not volume factors.

Topics: Animals; Blood Pressure; Body Weight; Cardiac Output; Dexamethasone; Dogs; Heart Rate; Hemodynamics; Hormones; Hypertension; Male; Neurosecretory Systems; Norepinephrine; Prazosin; Renal Circulation; Saralasin; Vascular Resistance

The hypotensive effects of three different angiotensin converting enzyme (ACE) inhibitors (captopril, enalapril, and lisinopril) and two angiotensin II (AII) analogues ([Sar1Ile5Ala8]AII and [Sar1Ile5Thr8]AII) were compared in conscious, freely-moving Brattleboro rats after 14 h of water deprivation. There was no difference between the hypotensive effects of the three ACE inhibitors. Neither was there any difference between the hypotensive effects of the two AII antagonists, although when administered following ACE inhibition, [Sar1Ile5Thr8]AII caused a transient pressor effect that was significantly less than that caused by [Sar1Ile5Ala8]AII. ACE inhibition caused a greater fall in blood pressure (BP) than AII antagonism and caused an additional fall in BP during AII antagonism. These results indicate an additional hypotensive effect of ACE inhibitors, over that of AII antagonists, that is not readily accounted for in terms of nonspecific effects of the former or agonistic properties of the latter.

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Body Weight; Captopril; Enalapril; Heart Rate; Lisinopril; Male; Rats; Rats, Brattleboro; Saralasin; Water Deprivation

The mechanisms whereby the pituitary gland maintains arterial pressure were investigated in rats. The arterial pressure in hypophysectomized rats was 30 mmHg below normal. Saralasin or captopril caused a further fall of 25 and 30 mmHg, respectively, suggesting that the renin-angiotensin system plays a role in blood pressure maintenance in hypophysectomized rats. Growth hormone administration to hypophysectomized rats increased the arterial pressure, but pretreatment with captopril prevented the effect. Plasma renin activity and basal renin secretion (in vitro) was normal in hypophysectomized rats despite a twofold greater renal renin content. Secretory responsiveness to isoproterenol and calcium omission was lower in hypophysectomized rats. It is concluded that the renin-angiotensin system plays a role in maintaining arterial blood pressure in hypophysectomized rats although the responsiveness of the system may be decreased.

Topics: Animals; Blood Pressure; Body Weight; Captopril; Growth Hormone; Hypophysectomy; Kidney; Male; Rats; Renin; Renin-Angiotensin System; Saralasin; Time Factors

The blood pressure response to different doses of methylprednisolone was examined in the rat. It is concluded that doses varying from 2.5 mg/kg/week to 20 mg/kg/week of this agent caused clear-cut elevations in arterial pressure. The methylprednisolone-induced arterial hypertension was accompanied by elevation in Plasma Renin Activity and administration of captopril or saralasin caused significant drops in systemic arterial pressure. Concomitant long term administration of captopril and methylprednisolone caused a delay in appearance and smaller elevations in arterial pressure. It is concluded the methylprednisolone in the rat causes arterial hypertension which is at least partially dependent upon renin angiotensin system activation. However elevated blood pressure levels were noticeable even during chronic captopril administration leading to the conclusion that other mechanism (s) may participate in the pathogenesis of this experimental model of hypertension in rats.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Body Weight; Captopril; Disease Models, Animal; Hypertension; Male; Methylprednisolone; Rats; Rats, Inbred Strains; Renin-Angiotensin System; Saralasin

1. The acute effects of the kallikrein inhibitor aprotinin (498 ki.u./min), and the kininase II inhibitor SQ 14,225 (250 MICROGRAM), GIVEN INTRAVEnously during saralasin-induced angiotensin blockade, were studied in conscious sham-operated rats and rats with benign and malignant two-kidney, one-clip Goldblatt hypertension during dietary sodium restriction. 2. The blood pressure of conscious sham-operated rats increased significantly in response to aprotinin. It remained unchanged after SQ 14,225 in contrast to the significant vasodepressor effect seen when SQ 14,225 was given to the same rats under surgical stress and pentobarbital anaesthesia. 3. Benignly hypertensive rats showed a consistent vasopressor response to aprotinin and a marked vasodepressor response to SQ 14,225. The effects of both inhibitors were markedly and significantly blunted in malignantly hypertensive rats. 4. Our demonstration that two agents with known opposite actions on the kallikrein-kinin system produced predictable and opposite effects on blood pressure may indicate that this system is involved in the homeostatic regulation of blood pressure. It may play an important antihypertensive role in benign two-kidney, one-clip Goldblatt hypertension, a role which might be impaired in malignant hypertension.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Aprotinin; Blood Pressure; Body Weight; Captopril; Homeostasis; Hypertension; Kallikreins; Kinins; Male; Proline; Rats; Renin; Saralasin

The effect of total adrenalectomy on the mechanisms of arterial pressure control was studied in uninephrectomized rats with and without renal artery stenosis (Goldblatt one-kidney model). Four groups of rats were prepared and maintained on high-salt intake (1% NaCl): uninephrectomized-KI; KI + adrenalectomy-KIAx; uninephrectomized with renal artery stenosis-GI; and GI with adrenalectomy-GIAx. Over 3 wk blood pressure rose significantly in both GI and GIAx but the degree of increase in GI was greater. Hyponatremia, hyperkalemia, and increased plasma urea nitrogen were observed in both KIAx and GIAx. Plasma renin concentration (PRC) and plasma renine activity (PRA) were markedly increased and plasma renin substrate (PRS) was decreased in both adrenalectomized groups. Infusion of saralasin resulted in significant and similar reductions in mean arterial pressure (MAP) in KIAx and GIAx, but had no effect on MAP in KI and GI. These results allow approximations of the contribution to total MAP of identifiable components, which are: the total adrenal component, the renin-angiotensin system component, which partially compensates for loss of the adrenal secretions, and the independent effect of the renal artery clip. Thus, a multifactorial analysis of GI hypertension is provided.

Topics: Adrenal Glands; Adrenalectomy; Angiotensin II; Animals; Blood Pressure; Blood Urea Nitrogen; Body Weight; Heart; Hypertension, Renal; Male; Nephrectomy; Organ Size; Potassium; Rats; Renal Artery Obstruction; Renin; Saralasin; Sodium

Topics: Angiotensin II; Animals; Blood Pressure; Body Weight; Dose-Response Relationship, Drug; Female; Furosemide; Hypertension; Hypertension, Renal; Rats; Rats, Inbred Strains; Renin; Saralasin; Species Specificity

The hypotensive effect of acute sodium volume depletion, produced by chlorthalidone and a low sodium diet, was inversely related to the plasma renin concentration (PRC) in 13 hypertensive patients of varying aetiology (r = 0.61; p less than 0.05); weight reduction induced by this therapy was not related to PRC (r = 0.12; p greater than 0.1). The angiotensin II antagonist 1-sar-8-ala-angiotensin II failed to reduce arterial pressure when the patients ingested 130 mEq sodium per day, but pressure fell when it was infused during sodium volume depletion, except when PRC remained low; the changes in pressure were related to the plasma renin level (r = 0.78; p less than o.005). The combined hypotensive response to acute sodium volume depletion and to angiotensin II blockade during sodium volume depletion was not related to PRC (r = 0.15; p greater than 0.1). The results demonstrate that acute sodium volume depletion caused similar weight loss in patients with high and low PRC values, and it would have had similar hypotensive effects but for angiotensin-induced vasoconstriction in the high renin patients. Since 1-sar-8-ala-angiotensin II also reduced arterial pressure in 6 patients during chronic diuretic therapy, angiotensin II must still induce vasoconstriction in these circumstances.

Topics: Adult; Angiotensin II; Blood Pressure; Body Weight; Chlorthalidone; Diet, Sodium-Restricted; Female; Humans; Hypertension; Male; Renin; Saralasin; Sodium

Five hypertensive haemodialysis patients have been infused with saralisin. The infusion appears to be a simple diagnostic test separating patients into two groups. First, there are those whose blood pressure does not fall with saralasin pre-dialysis, but does fall with weight removal during dialysis; the blood pressure in these patients can be controlled by a reduction in pre-dialysis weight. Second, there are those whose blood pressure does fall with saralasin either pre- or post-dialysis; their arterial pressure does not fall with weight removal, but can be controlled by anti-hypertensive drugs. In two of the patients who responded to saralasin, the mechanism of the high blood pressure appeared to change from volume dependency, partial or complete, with suppressed renin release, to angiotensin dependency, partial or complete, as weight was removed during dialysis. These patients illustrate the importance of the interaction between volume and the level of angiotensin II in the maintenance of hypertension.

Topics: Adult; Angiotensin II; Blood Pressure; Body Weight; Female; Humans; Hypertension; Male; Renal Dialysis; Renin; Saralasin; Time Factors