Effect of enalapril (MK-421), an orally active angiotensin I converting enzyme inhibitor, on blood pressure, active and inactive plasma renin, urinary prostaglandin E2, and kallikrein excretion in conscious rats

The angiotensin I converting enzyme (ACE) inhibitor enalapril (MK-421), at a dose of 1 mg/kg or more by gavage twice daily, effectively inhibited the pressor response to angiotensin I for more than 12 h and less than 24 h. Plasma renin activity (PRA) did not change after 2 or 4 days of treatment at 1 mg/kg twice daily despite effective ACE inhibition, whereas it rose significantly at 10 mg/kg twice daily. Blood pressure fell significantly and heart rate increased in rats treated with 10 mg/kg of enalapril twice daily, a response which was abolished by concomitant angiotensin II infusion. However, infusion of angiotensin II did not prevent the rise in plasma renin. Enalapril treatment did not change urinary immunoreactive prostaglandin E2 (PGE2) excretion and indomethacin did not modify plasma renin activity of enalapril-treated rats. Propranolol significantly reduced the rise in plasma renin in rats receiving enalapril. None of these findings could be explained by changes in the ratio of active and inactive renin. Water diuresis, without natriuresis and with a decrease in potassium urinary excretion, occurred with the higher dose of enalapril. Enalapril did not potentiate the elevation of PRA in two-kidney one-clip Goldblatt hypertensive rats. In conclusion, enalapril produced renin secretion, which was in part beta-adrenergically mediated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma renin activity, active and inactive renin concentrations, and their responses to beta 1-adrenoceptor blockade with metoprolol in hyperthyroidism

Plasma renin activity (PRA), plasma renin concentration (PRC), inactive renin concentration (IRC) and total renin concentration (TRC) were measured in 31 normal controls and in 8 patients with hyperthyroidism. TRC was determined as angiotensin I generated with sheep renin substrate after an acid activation of plasma. The angiotensin I of non-acidified plasma was expressed as PRC. IRC was calculated as TRC minus PRC. The mean values for PRA, PRC, IRC and TRC were significantly (P less than 0.05 to P less than 0.01) higher in the hyperthyroid patients than in the normal or euthyroid controls. The administration of a beta 1-adrenergic blocker, metoprolol (120 mg/day for 14 days), produced a significant (P less than 0.05 to P less than 0.01) fall in levels of T4, PRA and TRC, and reduced the active renin ratio calculated from PRC/TRC significantly (P less than 0.025), as compared to the pretreatment values. Our observations support the idea that the higher PRA in hyperthyroidism is due to an increased secretion of renin. Furthermore, the results may indicate that the conversion of inactive to active renin is accelerated in hyperthyroidism, possibly by an increased sympathetic activity.     

Effect of indomethacin on the adrenal renin response to nephrectomy in the rat

The role of prostaglandins in the control of adrenal renin in vivo was evaluated in nephrectomized rats. Nephrectomy increased adrenal renin from 13.2 +/- 1.37 ng angiotensin I/mg protein/hr to 166.5 +/- 17.3 ng angiotensin I/mg protein/hr. Indomethacin treatment significantly suppressed the adrenal renin response to nephrectomy. (47.8 +/- 5.22 ng angiotensin I/mg protein/hr). Adrenal aldosterone was also suppressed by indomethacin. Adrenal prostaglandin E2 increased after nephrectomy and decreased after indomethacin. Plasma corticosterone and serum potassium did not change after indomethacin. These data indicate that inhibition of prostaglandin synthesis by indomethacin partially blocks the adrenal renin response to nephrectomy, suggesting that prostaglandins may play a role in the adrenal response to nephrectomy.     

Effect of indomethacin on the adrenal renin response to nephrectomy in the rat

The role of prostaglandins in the control of adrenal renin in vivo was evaluated in nephrectomized rats. Nephrectomy increased adrenal renin from 13.2 ± 1.37 ng angiotensin I/mg protein/hr to 166.5 ± 17.3 ng angiotensin I/mg protein/hr. Indomethacin treatment significantly suppressed the adrenal renin response to nephrectomy. (47.8 ± 5.22 ng angiotensin I/mg protein/hr). Adrenal aldosterone was also suppressed by indomethacin. Adrenal prostaglandin E₂ increased after nephrectomy and decreased after indomethacin.Plasma corticosterone and serum potassium did not change after indomethacin. These data indicate that inhibition of prostaglandin synthesis by indomethacin partially blocks the adrenal renin response to nephrectomy, suggesting that prostaglandins may play a role in the adrenal response to nephrectomy.     

Does heparin inhibit renin activity?

Although heparin was reported in the 1960s to inhibit renin activity, this has not always been confirmed by other investigators. Hence, we re-examined whether heparin really inhibits renin or not. Renin activities were determined by radioimmunoassay of angiotensin I generated at pH 7.4. (i) No significant difference was found between the two kinds of plasma samples obtained with heparin and with EDTA as anticoagulant, in ARC (renin activity with addition of sheep renin substrate), TRC (ARC after activation of inactive renin by trypsin), or PRA (plasma renin activity without additional substrate). (ii) Even in higher concentrations of heparin up to 500 U/mL, neither PRA, ARC, nor TRC of plasma was affected significantly. (iii) Heparin, in concentrations up to 500 U/mL, exerted no significant effect on TRC of the media of human vascular smooth muscle cell culture. In conclusion, heparin does not exert any significant inhibitory effect on human renin nor does it affect activation of inactive renin by trypsin in the range of concentration of practical use, under the conditions employed in this study.     

Parathyroid hormone-related protein stimulates plasma renin activity via its anorexic effects on sodium chloride intake

Parathyroid hormone-related protein (PTHrP) increases renin release from isolated perfused kidneys and may act as an autacoid regulator of renin secretion, but its effects on renin in vivo are unknown. In vivo, PTHrP causes hypercalcemia and anorexia, which may affect renin. We hypothesized that chronically elevated PTHrP would increase plasma renin activity (PRA) indirectly via its anorexic effects, reducing sodium chloride (NaCl) intake and causing NaCl restriction. We infused male Sprague-Dawley rats with the vehicle (control) or 125 μg PTHrP/day (PTHrP) via subcutaneous osmotic minipumps for 5 days. To replenish NaCl consumption, a third group of PTHrP-infused rats received 0.3% NaCl (PTHrP + NaCl) in their drinking water. PTHrP increased PRA from a median control value of 3.68 to 18.4 ng Ang I·ml(-1)·h(-1) (P < 0.05), whereas the median PTHrP + NaCl PRA value was normal (7.82 ng Ang I·ml(-1)·h(-1), P < 0.05 vs. PTHrP). Plasma Ca(2+) (median control: 10.2 mg/dl; PTHrP: 13.7 mg/dl; PTHrP + NaCl: 14.1 mg/dl; P < 0.05) and PTHrP (median control: 0.03 ng/ml; PTHrP: 0.12 ng/ml; PTHrP + NaCl: 0.15 ng/ml; P < 0.05) were elevated in PTHrP- and PTHrP + NaCl-treated rats. Body weights and caloric consumption were lower in PTHrP- and PTHrP + NaCl-treated rats. NaCl consumption was lower in PTHrP-treated rats (mean Na(+): 28.5 ± 4.1 mg/day; mean Cl(-): 47.8 mg/day) compared with controls (Na(+): 67.3 ± 2.7 mg/day; Cl(-): 112.8 ± 4.6 mg/day; P < 0.05). NaCl consumption was comparable with control in the PTHrP + NaCl group; 0.3% NaCl in the drinking water had no effect on PRA in normal rats. Thus, our data support the hypothesis that PTHrP increases PRA via its anorexic effects, reducing NaCl intake and causing NaCl restriction.     

Prostaglandins that increase renin production in response to ACE inhibition are not derived from cyclooxygenase-1

It is well known that nonselective, nonsteroidal anti-inflammatory drugs inhibit renal renin production. Our previous studies indicated that angiotensin-converting enzyme inhibitor (ACEI)-mediated renin increases were absent in rats treated with a cyclooxygenase (COX)-2-selective inhibitor and in COX-2 -/- mice. The current study examined further whether COX-1 is also involved in mediating ACEI-induced renin production. Because renin increases are mediated by cAMP, we also examined whether increased renin is mediated by the prostaglandin E(2) receptor EP(2) subtype, which is coupled to G(s) and increases cAMP. Therefore, we investigated if genetic deletion of COX-1 or EP(2) prevents increased ACEI-induced renin expression. Age- and gender-matched wild-type (+/+) and homozygous null mice (-/-) were administered captopril for 7 days, and plasma and renal renin levels and renal renin mRNA expression were measured. There were no significant differences in the basal level of renal renin activity from plasma or renal tissue in COX-1 +/+ and -/- mice. Captopril administration increased renin equally [plasma renin activity (PRA): +/+ 9.3 +/- 2.2 vs. 50.1 +/- 10.9; -/- 13.7 +/- 1.5 vs. 43.9 +/- 6.6 ng ANG I x ml(-1) x h(-1); renal renin concentration: +/+ 11.8 +/- 1.7 vs. 35.3 +/- 3.9; -/- 13.0 +/- 3.0 vs. 27.8 +/- 2.7 ng ANG I x mg protein(-1) x h(-1); n = 6; P < 0.05 with or without captopril]. ACEI also increased renin mRNA expression (+/+ 2.4 +/- 0.2; -/- 2.1 +/- 0.2 fold control; n = 6-10; P < 0.05). Captopril led to similar increases in EP(2) -/- compared with +/+. The COX-2 inhibitor SC-58236 blocked ACEI-induced elevation in renal renin concentration in EP(2) null mice (+/+ 24.7 +/- 1.7 vs. 9.8 +/- 0.4; -/- 21.1 +/- 3.2 vs. 9.3 +/- 0.4 ng ANG I x mg protein(-1) x h(-1); n = 5) as well as in COX-1 -/- mice (SC-58236-treated PRA: +/+ 7.3 +/- 0.6; -/- 8.0 +/- 0.9 ng ANG I x ml(-1) x h(-1); renal renin: +/+ 9.1 +/- 0.9; -/- 9.6 +/- 0.5 ng ANG I x mg protein(-1) x h(-1); n = 6-7; P < 0.05 compared with no treatment). Immunohistochemical analysis of renin expression confirmed the above results. This study provides definitive evidence that metabolites of COX-2 rather than COX-1 mediate ACEI-induced renin increases. The persistent response in EP(2) nulls suggests involvement of prostaglandin E(2) receptor subtype 4 and/or prostacyclin receptor (IP).     

Increased renin excretion is associated with augmented urinary angiotensin II levels in chronic angiotensin II-infused hypertensive rats

Renin expression in principal cells of collecting ducts (CD) is upregulated in angiotensin II (ANG II)-dependent hypertensive rats; however, it remains unclear whether increased CD-derived renin undergoes tubular secretion. Accordingly, urinary levels of renin (uRen), angiotensinogen (uAGT), and ANG II (uANG II) were measured in chronic ANG II-infused Sprague-Dawley rats (80 ng/min for 14 days, n = 10) and sham-operated rats (n = 10). Systolic blood pressure increased in the ANG II rats by day 5 and continued to increase throughout the study (day 13; ANG II: 175 ± 10 vs. sham: 116 ± 2 mmHg; P < 0.05). ANG II infusion increased renal cortical and medullary ANG II levels (cortical ANG II: 606 ± 72 vs. 247 ± 43 fmol/g; P < 0.05; medullary ANG II: 2,066 ± 116 vs. 646 ± 36 fmol/g; P < 0.05). Although plasma renin activity (PRA) was suppressed in the ANG II-infused rats (0.3 ± 0.2 vs. 5.5 ± 1.8 ng ANG I·ml(-1)·h(-1); P < 0.05), renin content in renal medulla was increased (12,605 ± 1,343 vs. 7,956 ± 765 ng ANG I·h(-1)·mg(-1); P < 0.05). Excretion of uAGT and uANG II increased in the ANG II rats [uAGT: 1,107 ± 106 vs. 60 ± 26 ng/day; P < 0.0001; uANG II: 3,813 ± 431 vs. 2,080 ± 361 fmol/day; P < 0.05]. By day 13, despite suppression of PRA, urinary prorenin content increased in ANG II rats [15.7 ± 3 vs. 2.6 ± 1 × 10(-3) enzyme units excreted (EUE)/day, P < 0.01] as was the excretion rate of renin (8.6 ± 2 × 10(-6) EUE/day) compared with sham (2.8 ± 1 × 10(-6) EUE/day; P < 0.05). Urinary renin and prorenin protein levels examined by Western blot were augmented ～10-fold in the ANG II-infused rats. Concomitant AT(1) receptor blockade with candesartan prevented the increase. Thus, in ANG II-dependent hypertensive rats with marked PRA suppression, increased urinary levels of renin and prorenin reflect their augmented secretion by CD cells into the luminal fluid. The greater availability of renin and AGT in the urine reflects the capability for intratubular ANG II formation which stimulates sodium reabsorption in distal nephron segments.     

Effects of angiotensin I-converting enzyme inhibitor, SQ 14225, in nomal men.

Effects of an orally active angiotensin I-converting enzyme inhibitor, SQ 14225, on the actions of angiotensin I (AI) infused intravenously for 120 to 390 min were studied in 5 normal men. When 20 ng/kg/min of AI infusion was started immediately after a single oral administration of 100 mg of SQ 14225, a significant rise in blood pressure (BP) was observed for the first 15 min, but BP began to fall from 17 min and returned to the pretreatment level at 45 min. This BP level continued at least to 120 min and in one subject to 180 min. In this subject BP began to rise again from 185 min and reached the level of 15 min at 390 min. Plasma AI level increased gradually from 45 min. At 15 min plasma renin activity (PRA) decreased and plasma aldosterone (PA) increased, but then PRA began to increase and PA began to decrease. At 120 min the values of PRA and PA were similar to the pretreatment values. In one subject plasma AI and PRA began to decrease and PA began to increase after 120 or 180 min. On the other hand, in the 5 men sole AI infusion caused a continued BP rise, PRA decrease and PA increase, and sole SQ 14225 administration caused increases in plasma AI and PRA and a decrease in PA but no BP change. From these results it was concluded that complete blockade and partial inhibition of AI conversion by 100 mg of oral SQ 14225 lasted for about 2.5 and 6.5 hr, respectively and that BP rise, PRA suppression and aldosterone stimulation after AI infusion were entirely due to the actions of angiotensin II converted from AI.     

Effects of an angiotensin II antagonist; [sarcosine 1, isoleucine 8] angiotensin II, on blood pressure, plasma renin activity and plasma aldosterone concentration in hypertensive and normotensive subjects taking oral contraceptives.

To examine the involvement of renin-angiotensin-aldosterone system in the etiology of oral contraceptive induced hypertension, normal women (Group I), normotensive (Group II) and hypertensive (Group III) women taking Ovulen (R) were infused with a competitive angiotensin II (AII) antagonist, [1-sarcosine, 8-isoleucine] angiotensin II. The angiotensin II antagonist was infused at a rate of 600 ng/kg/min for 30 min 1.5 hrs after intravenous injection of 40 mg of furosemide. Blood pressure was monitored and pre-infusion and post-infusion plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were determined. Pre-infusion PRA and PAC showed no significant differences among these three groups. In response to the AII antagonist infusion blood pressure rose in Groups I and II, but blood pressure responses in Group III were variable. Four out of the total 6 subjects had pressor responses and only one subject had a significant blood pressure reduction. In both Groups I and II, PRA decreased and PAC rose after infusion of the antagonist. In Group III, PRA decreased to a lesser degree and PAC showed no consistent change. These data suggest that the renin-angiotensin-aldosterone system in hypertensive women or oral contraceptives is different from that of the normotensive users. However, the pathophysiology of oral contraceptive induced hypertension is not homogenous and angiotensinogenic hypertension is uncommon.     

Changes in activity of the renin-angiotensin system of the rat by induction of acute inflammation

Angiotensinogen is the precursor of biologically active peptide angiotensin II and its hepatic synthesis is increased by the induction of acute inflammation. Studies were carried out to know whether the rise in plasma angiotensinogen is actually involved in the activity of the renin-angiotensin system during acute inflammation. The plasma level of angiotensinogen in rats was increased to 2.5 times the normal level 16 h after the induction of acute inflammation by administration of lipopolysaccharide (LPS). The plasma renin concentration (PRC) was decreased to about 40% of the normal level concomitantly with a reduction of plasma renin activity (PRA) at 4 h after LPS administration. In contrast, 16 h after LPS injection, when plasma angiotensinogen showed a high level and PRC had recovered to the normal range, PRA was increased to 1.7 times the normal level. These results indicate that acute inflammation induced by LPS causes a biphasic change in the generation of angiotensin I, i.e., an early decrease depending upon the reduction of PRC and later increase depending upon elevation of the angiotensinogen concentration.     

Effect of aldosterone on vascular angiotensin II receptors in the rat

The effect of aldosterone on the density and affinity of binding sites for 125I-labelled angiotensin II was investigated in a particulate fraction prepared from the rat mesenteric arteriolar arcades. The infusion of aldosterone 6.6 micrograms/h intraperitoneally via Alzet osmotic minipumps for 6 d produced an increase in the density of binding sites for 125I-labelled angiotensin II without change in affinity. After sodium depletion, mesenteric artery angiotensin II receptors were down-regulated as expected. An increase in the number of binding sites could be found when aldosterone was infused into sodium-depleted rats with no change in the elevated plasma renin activity. The intraperitoneal infusion of angiotensin II (200 ng X kg-1 X min-1 for 6 d) simultaneously with aldosterone resulted in down-regulation of vascular angiotensin II receptors, whereas after intravenous angiotensin II infusion (at 60 ng X kg-1 X min-1) the density of angiotensin II binding sites rose with aldosterone infusion. Plasma renin activity (PRA) was reduced and plasma angiotensin II increased in a dose-dependent fashion after angiotensin II infusion. An aldosterone concentration of 3 ng/mL for 18 h produced an increase in the number of angiotensin II binding sites in rat mesenteric artery smooth muscle cells in culture. We conclude that increased plasma aldosterone may result in up-regulation of vascular angiotensin II receptors independently of changes in plasma renin activity, and may in certain physiological states effectively antagonize the down-regulating action of angiotensin II.     

Mechanism for the increase in plasma renin activity by pentobarbital anesthesia

The mechanism by which pentobarbital anesthesia causes increases in plasma renin activity (PRA) was examined in dogs infused with either propranolol or indomethacin, an inhibitor of prostaglandin synthetase. Infusion of propranolol at 1 mg/kg, (I.V.) followed by 0.6–0.7 mg/kg/hr decreased PRA from 6.98±2.49 ng/m1/hr during control periods to 1.58±0.79 ng/m1/hr 30 minutes after the injection of propranolol (P<0.025). Subsequent induction of anesthesia with sodium pentobarbital caused PRA to rise to 3.87±0.93 ng/m1/hr in 30 minutes. (P<0.01). Plasma potassium concentration decreased from 4.6±0.2 mEq/L to reach 4.0±0.1 mEq/L 30 minutes after induction of anesthesia (P<0.005). Infusion of indomethacin at 5 mg/kg, (I.V.) followed by 1.5 ? 3.1 mg/kg/hr into conscious dogs did not decrease PRA. In contrast to the report by Montgomery et al (Fed. Proc. 36: 989, 1977), we found that the increase in PRA after pentobarbital anesthesia could not be blocked by indomethacin. PRA was 5.3±1.2 ng/m1/hr(M ± SEM) during control periods and was 4.7±1.4 ng/m1/hr 30 minutes after the infusion of indomethacin (P<0.1). PRA increased to 10.9±2.3 ng/m1/hr, 9.2±2.2 ng/m1/hr, and 7.7±1.7 ng/m1/hr at 5, 15 and 30 minutes, respectively, after the administration of pentobarbital (P<0.005, P<0.025, P<0.05). PRA declined to 4.2±1.3 ng/m1/hr 60 minutes after pentobarbital anesthesia (P<0.1). It is concluded that the mechanism by which pentobarbital causes increases in PRA is independent of prostaglandins.     

Renin and Angiotensin-Converting Enzyme in Human Neuroblastoma Tissue

High activity of renin was demonstrated in human neuroblastoma tissue. This activity was inhibited by specific antibody raised against human renal renin, indicating that it was not due to the nonspecific action of proteases. The specific activity of renin was 122.8 ng of angiotensin I generated mg of protein-1 h-1. It shared some biochemical features with well-known kidney renin, such as molecular weight, optimum pH, the presence of trypsin-activatable inactive renin, and glycoprotein nature. Furthermore, angiotensin-converting enzyme (ACE) activity (2.64 nmol mg of protein-1 min-1) was found in the tissue. This activity was inhibited by captopril, a specific ACE inhibitor, or by omission of chloride ion. These results suggest that true renin in addition to ACE exists in human neuroblastoma tissue.     

Biological activities of sarcosine1-angiotensin I in man

In order to examine whether substrate specificity of angiotensin-converting enzyme (ACE) exists or not for N-terminal substituted angiotensin I (ANG I) in man, biological activities of sarcosine1-angiotensin I (Sar1-ANG I) and the effects of an ACE inhibitor, captopril, on the Sar1-ANG I activities were studied in 5 normal men. The following 3 experiments were done at 1 week intervals. Sarcosine1-angiotensin II (Sar1-ANG II) was infused iv at a rate of 5 pmol/kg X min from 0900 h to 0930 h in 5 normal men in a recumbent position. Blood pressure rose remarkably and the average increment was 38/31 mmHg at 30 min (p less than 0.001). Average duration of the pressor action after the cessation of the infusion (T) was 40 min for systolic and 50 min for diastolic and much longer than T of isoleucine5-angiotensin II. Plasma renin activity (PRA) decreased (p less than 0.01) and plasma aldosterone (PA) increased significantly (p less than 0.01). Sar1-ANG I was infused iv at a rate of 5 pmol/kg X min from 0900 h to 0930 h. Blood pressure rose to the same extent as in (1) (p less than 0.001). T was 40 min for both systolic and diastolic and much longer than T of ANG I in man. PRA decreased (p less than 0.01) and PA increased (p less than 0.01) significantly. Oral 100 mg captopril was given at 08:00 h and Sar1-ANG I was infused iv at a rate of 5 pmol/kg X min from 09:00 h to 09:30 h.(ABSTRACT TRUNCATED AT 250 WORDS)     

Biochemical evidence for existence of immunoreactive renin in human prolactinoma tissue

High activity of renin was demonstrated in human prolactinoma tissue. This activity was almost completely inhibited by specific antibody raised against human renal renin, indicating that it was not due to the nonspecific action of proteases. The specific activity of renin was 5.04 ng of angiotensin I generated/mg of protein per h, comparable to that of the pituitary tissue prepared from postmortem human subjects. The biochemical properties of the prolactinoma renin were generally similar to those of well-known kidney enzyme, such as molecular mass (Mr = 46,000), optimum pH (6.0), and glycoprotein nature. However, the isoelectric points (pI) of the prolactinoma renin (pI = 4.90, 5.04, 5.24 and 5.41) differed somewhat from those of plasma and kidney renins reported hitherto. These results indicate that true renin can be produced in human prolactinoma tissue.     

Rat ovarian angiotensin II receptors, renin, and angiotensin I-converting enzyme during pregnancy and the postpartum period.

The ovarian renin-angiotensin system (RAS) has been studied extensively in the virgin cycling rat, but little information is available about this system in pregnant and postpartum rats. We show that renin and angiotensin I-converting enzyme (ACE)--the key enzymes involved in angiotensin II (Ang II) formation--and Ang II receptors, are present in pregnant and postpartum rat ovaries. From gestation Days 2-4 to 10-12, active ovarian renin ranged from 1.12 +/- 0.13 to 1.27 +/- 0.19 ng Ang I/h/mg and comprised between 68 and 86% of total (active+inactive) ovarian renin activity. Between Days 10-12 and Days 14-16 of pregnancy, ovarian active renin activity increased slightly, but inactive renin disappeared, suggesting its activation; the remaining active renin then decreased 62% by Days 18-20 (p < 0.05). On postpartum Day 2, both active and total ovarian renin activity exceeded that of Days 2-20 of pregnancy (p < 0.05); levels of both then declined sharply by postpartum Day 3 (p < 0.05). In pregnant rats, levels of ovarian Ang II receptors, identified by the specific binding of [125I]-[Sar1,Ile8]Ang II to ovarian membranes, were high between Days 2-4 and 10-12 of pregnancy, ranging from 12.8 +/- 1.7 to 15.7 +/- 3.4 fmol/mg, but steadily declined by 82% between gestation Days 10-12 and 18-20 (p < 0.05). Postpartum Ang II receptor levels on Days 2, 3, and 4 showed a gradual increase from low levels comparable to Days 18-20 of pregnancy. Ovarian ACE activity did not change throughout pregnancy or during the postpartum period.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunohistochemical renin study of DES-induced renal tumor in the Syrian hamster

Diethylstilbestrol (DES) treatment of a male Syrian hamster resulted in the development of a renal tumor and its widely scattered serosal metastases. Cells in both the primary tumor and metastatic nodules contained secretory granules. The tumors were transplanted serially into DES-supported and non-DES-supported host hamsters until DES-independent tumors developed. Rabbit antiserum to mouse salivary renin and rabbit antiserum to rat kidney resin were reacted with sections of the primary tumor, metastatic nodules, and all transport tumors. The sections were stained by the PAP and Vector-ABC-AP procedures. Renin-positive material was observed in all tumors. Plasma renin activity (PRA) was determined for the host hamsters carrying the renal tumor transplants and compared to the PRA values that had been determined for normal non-DES-treated male and female hamsters. It was found that the average PRA values of host hamsters carrying the tumor transplants were significantly higher than the normal PRA values.     

Regulation of renin angiotensins by gonadotropic hormones in cultured murine Leydig tumor cells. Release of angiotensin but not renin

Renin and angiotensins coexist in various tissues. The mode of control of the extrarenal renin-angiotensin system is not clear. Whether it is renin or angiotensin that is secreted has not been identified. We have investigated gonadotropin-dependent synthesis and subsequent release of the components of the intracellular renin-angiotensin system in a cloned and cultured mouse Leydig tumor cell line (MA-10). Treatment of cultured Leydig cells with bovine luteinizing hormone (bLH, 100 ng/ml) or human chorionic gonadotropin (hCG, 25 ng/ml) resulted in greater than 150- and 40- fold increased formation of angiotensin I and angiotensin II. In cells incubated with bLH or hCG, the majority of AII (up to 90%) was found in the culture medium while most of angiotensin I (greater than 85%) was in the cell lysate. Treatment with gonadotropic hormones (bLH/ hCG) increased renin 35- to 40-fold. Renin activity was confined mainly in the cell lysate even after the stimulation by gonadotropins, and only 1-2% of the total renin activity was detectable in culture medium. These results were interpreted that, in these transformed cells, hormonally-induced renin functions to generate angiotensin I within the Leydig cell and it is the angiotensins which are secreted.