Biomedical subjects

J E Sealey

Publications and source records attributed to J E Sealey.

At least 55 records · Page 3Linked to original sources

PubMed1992

Inhibition of human renin by rat plasma. Rat angiotensinogen is a competitive inhibitor of the human renin-substrate interaction.

Human renin can cleave rat angiotensinogen, yet infusion of human renin into rats causes only a modest increase in blood pressure. We therefore investigated whether there is a factor in rat plasma which inhibits human renin activity. The addition of 20% normal rat plasma to human plasma had a slight, but not significant, inhibitory effect on the rate of angiotensin formation, while nephrectomized rat plasma, which had a seven-fold higher concentration of angiotensinogen, caused a dose dependent inhibition (20 to 70%). The rat plasma inhibitor copurified with angiotensinogen. Analysis of the kinetics of the human renin-human substrate reaction and of the human renin-rat substrate reaction revealed that the rate of angiotensin I production in the presence of both substrates could be entirely accounted for by assuming that rat and human angiotensinogens are competitive inhibitors of each other. These results show that human renin can cleave rat substrate but the reaction rate is extremely slow relative to the cleavage of human angiotensinogen. They also indicate that rat angiotensinogen is an effective competitive inhibitor of the human renin-substrate reaction. These results may be relevant to the development of renin inhibitors and to transfection studies involving heterologous renin or substrate genes.

Angiotensinogen↗

PubMed1992

Highest concentrations of prorenin and human chorionic gonadotropin in gestational sacs during early human pregnancy.

Prorenin is not only the biosynthetic precursor of renin; under certain circumstances in vitro prorenin exhibits reversible intrinsic renin activity and can form angiotensin from renin substrate with or without cleavage of the prosequence. Prorenin is the predominant form of renin synthesized by reproductive organs (ovary, chorion laeve of the placenta, uterine decidua). Its plasma concentrations increases 10-fold throughout pregnancy to 10-100 times that of renin; amniotic fluid prorenin concentration is even higher. No data are available of gestational fluid prorenin concentrations during early pregnancy. For the first 10 weeks there are two gestational cavities; the chorionic cavity then disappears and the smaller amniotic cavity becomes predominant. In this study we measured prorenin, renin, renin substrate and hCG in fluid aspirated from gestational sacs during the first trimester of gestation (predominantly chorionic) and during the second and third trimesters (amniotic). Seventeen patients had amniocentesis during the second or third trimester. Nine patients underwent selective abortion of multiple pregnancy at 7-12 weeks gestation. One patient underwent surgery at 5 5/7 weeks (26 days after conception) for a tubal pregnancy. Second and third trimester amniotic fluid prorenin maximum velocity (Vmax) (16 and 3 sacs, respectively) averaged 6,100 +/- 1,700 (SD) and 1,930 +/- 760 ng/mL.h, respectively (i.e. 1,700 and 540 ng/L.s). In gestational fluid collected before 8 weeks, prorenin Vmax was 10-fold higher, averaging 62,500 +/- 40,000 ng/mL.h (17,000 ng/L.s). The concentration was 140,000 ng/mL.h (39,000 ng/L.s) in the 5 5/7 week tubal pregnancy. In sharp contrast, at 10-12 weeks gestation (n = 3) prorenin Vmax was only 260 +/- 114 ng/mL.h (72 ng/L.s); human CG was also highest before 8 weeks (276,500 +/- 110,900 IU/L) and lowest at 10-12 weeks (1210 +/- 540 IU/L) with intermediate levels occurring later in pregnancy. This study shows that the highest biological levels of prorenin yet detected (close to 1 micrograms protein/mL) occur in gestational sacs in early pregnancy, consistent with a role for the renin-angiotensin system in embryonic development or placentation.

Amnion↗

PubMed1992

Localization of renin gene expression to monkey ovarian theca cells by in situ hybridization.

To investigate the sites of renin gene expression and localization of renin in primate ovaries, five cynomolgus (Macaca fascicularis) and one rhesus (Macaca mulatta) monkey were treated with gonadotropins to induce multiple follicle development. One ovary was removed before hCG injection (1200 IU) from three monkeys and one ovary was removed 36 h after hCG administration from three monkeys. In three monkeys, the remaining ovary was removed 3, 5, and 7 days after injection of hCG. To detect and localize renin messenger RNA, 35S-radiolabelled 1.1 kb length complementary DNA and RNA probes of human renin were used for in situ hybridization. To compare the synthesis with the presence and the storage of renin or prorenin, renin antigen was assessed by immunohistochemistry in the same tissues using a polyclonal antibody against human renin (R15). Renin mRNA was detected by in situ hybridization only in ovaries collected within 5 days of exposure to hCG. All such ovaries exhibited a positive signal. Renin mRNA was localized to the theca interna and theca lutein cells. Positive cells were observed in a few growing antral follicles, in occasional mature preovulatory follicles, in corpus luteum, and most strikingly in atretic follicles. No signal was detected in primordial, primary, or in small antral follicles of ovaries exposed to hCG. In contrast with the in situ hybridization data, no signal was detected by immunohistochemistry using antirenin antibodies which exhibited a positive signal in monkey kidney. These results indicate that hCG turns on renin gene expression. Renin is synthesized without significant intracellular storage in monkey ovarian theca interna cells and in corpus luteum. The absence of storage of renin is consistent with the high concentrations of prorenin found in ovarian follicular fluid of hCG stimulated primates and with our knowledge of cellular renin processing which indicate that prorenin is secreted constitutively as it is synthesized.

Animals↗

PubMed1992

Angiotensin II receptor antagonist delays renal damage and stroke in salt-loaded Dahl salt-sensitive rats.

OBJECTIVE: To study the effects of blockade of the renin-angiotensin system upon the development of hypertension, end-organ damage and mortality in Dahl salt-sensitive (DSS) rats using an angiotensin II receptor antagonist, losartan. DESIGN AND METHODS: DSS rats (n = 186) were fed 8% NaCl from 6 to 16 weeks of age. One group received losartan whilst the control group was untreated. Changes in blood pressure and plasma renin activity (PRA), as well as renal and cerebrovascular damage and survival were assessed during the study. RESULTS: Losartan blunted the blood pressure rise only transiently. Salt loading suppressed PRA in both groups until week 4 and thereafter it rose more markedly in the treated group. With no treatment renal lesions were first detected at 2 weeks, and strokes at 6 weeks. However, losartan transiently decreased the incidence and delayed the progression of renal damage and cerebrovascular lesions (strokes) and increased survival. PRA correlated with renal damage and the incidence of strokes in both groups. Blood pressure only partially affected survival, but did not correlate with stroke incidence. CONCLUSIONS: These results indicate that whereas the rise in blood pressure is dependent upon sodium loading, morbidity and mortality in salt-loaded DSS rats are associated with activation of the renin-angiotensin system and are only partially related to blood pressure.

Angiotensin II↗

PubMed1991

Association of the renin-sodium profile with the risk of myocardial infarction in patients with hypertension.

BACKGROUND: To test the prognostic value of plasma renin activity prospectively, we determined the pretreatment renin-sodium profile of 1717 subjects with mild-to-moderate hypertension (mean age, 53 years; 36 percent white; 67 percent men) in a systematic work-site treatment program. METHODS: Renin profiles, obtained by plotting plasma renin activity against the urinary excretion of sodium, were classified as high (12 percent of the subjects), normal (56 percent), and low (32 percent), and there were expected variations according to age, sex, and race. Modified stepped-care treatment for hypertension, prescribed without reference to the renin profile, was similar in the three renin groups. RESULTS: Mean (+/- SD) blood pressure at entry was 151 +/- 19/100 +/- 10 mm Hg in the subjects with a high renin profile, 151 +/- 19/97 +/- 10 mm Hg in those with a normal profile, and 151 +/- 20/96 +/- 11 mm Hg in those with a low profile. During 8.3 years of follow-up, there were 27 myocardial infarctions. As adjusted for age, sex, and race, the incidence of myocardial infarction per 1000 person-years was 14.7 among the subjects with a high renin profile, 5.6 among those with a normal profile, and 2.8 among those with a low profile (rate ratio for high vs. low, 5.3; 95 percent confidence interval, 3.4 to 8.3). The rate of mortality from all causes was 9.3 in the high-profile group, 5.3 in the normal-profile group, and 3.9 in the low-profile group. The independent association of a high renin profile with myocardial infarction (but not with stroke or noncardiovascular events) was affirmed by Cox analyses (rate ratio for high vs. normal plus low, 3.2; 95 percent confidence interval, 1.2 to 8.4) after adjustment for race, sex, age at entry, serum cholesterol level, smoking status, electrocardiographic evidence of left ventricular hypertrophy, blood glucose level, body-mass index, history of cardiovascular disease or treatment, blood pressure, and use of beta-blockers. CONCLUSIONS: In the study population, whose blood pressure before and during treatment was in a narrow range, and after other cardiovascular risk factors had been considered, the renin profile before treatment remained independently associated with the subsequent risk of myocardial infarction.

Blood Pressure↗

PubMed1991

Increased plasma prorenin but not renin after bilateral ureteral ligation in dogs.

Plasma prorenin is normally higher than renin and usually changes in response to the same stimuli. In dogs, plasma prorenin and renin disappear after bilateral nephrectomy, indicating that both are of renal origin. It has been proposed that prorenin may mediate tissue renin systems via its reversible intrinsic renin-like activity. The renin-angiotensin system has been implicated in the changes in renal function that occur with bilateral ureteral obstruction, but plasma prorenin has not been investigated. We therefore studied the effect of 48-hour bilateral obstruction on plasma prorenin in two groups of dogs: one was volume expanded (N = 5), while the other group (N = 6) was euvolemic. Plasma prorenin concentration increased fourfold in both groups, angiotensinogen increased twofold, while plasma renin activity was unchanged. Following release of obstruction, plasma renin fell slightly while prorenin and angiotensinogen remained elevated. There was a positive relationship between plasma prorenin and renin before (r = 0.63, P less than 0.05) and after (r = 0.76, P less than 0.01) obstruction. Post-obstruction, ERPF and GFR were subnormal but filtration fraction was maintained; the higher the ERPF and GFR the higher the plasma prorenin post-obstruction (r = 0.83, P less than 0.01 and r = 0.77, P less respectively; N = 11). These results show that impairment of renal function during bilateral obstruction is associated with an increase in plasma prorenin but not renin. Nonetheless, there is a positive relationship between plasma prorenin and renin both pre- and post-obstruction. Thus, preferential impairment of clearance of prorenin relative to renin may occur during bilateral obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗

PubMed1991

The greater renin system. Its prorenin-directed vasodilator limb. Relevance to diabetes mellitus, pregnancy, and hypertension.

A greater renin system is proposed. Evidence is presented that a greater renin system exists that has both vasodilator and vasoconstrictor properties. Vasodilator activity is induced by prorenin, vasoconstrictor activity by renin. Our model is based on evidence that both prorenin and renin have the capacity to generate angiotensin and that angiotensin causes vasodilation at high concentrations and vasoconstriction at low concentrations. In our model, prorenin acts only at particular target sites while renin of renal origin acts via the general circulation. Prorenin's designation as a biosynthetic precursor implies lack of intrinsic catalytic activity whereas in fact it can become reversibly active. Activation may occur in vivo at binding sites without cleavage of the prosequence. In this framework, prorenin should be more aptly called renin I and circulating active renin, renin II. In our model, the role of renin I (prorenin) is to generate localized high concentrations of angiotensin II, eg, in the afferent arteriole of the kidney and in other vital organs, causing regional dilation by rendering tissues insensitive (tachyphylactic) to the vasoconstrictor effect of circulating angiotensin II or by releasing vasodilator substances. The role of renin II (active renin) is to constrict resistance vessels and the efferent arteriole of the kidney, thereby raising blood pressure, maintaining glomerular filtration rate, and enabling more blood flow to those organs that selectively bind prorenin. This twin control system is ideally designed to maintain blood flow to vital organs.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

PubMed1991

Tissue renin and prorenin increase in female cats during the reproductive cycle without commensurate changes in plasma, amniotic or ovarian follicular fluid.

The renin gene is expressed, primarily as prorenin, in the ovary, uterus and placenta. High concentrations of prorenin are present in human ovarian follicular and amniotic fluids and ovarian secretion causes increases in plasma prorenin at mid-menstrual cycle and during pregnancy. Plasma prorenin is low but detectable in nephrectomized human subjects. Comparative studies in female cats revealed several differences. Cat plasma prorenin became undetectable after bilateral nephrectomy. Neither plasma prorenin nor renin increased during pregnancy. Renin and prorenin were undetectable in ovarian follicular, amniotic and allantoic fluids. Human chorionic gonadotropin-induced ovulation caused only small increases in plasma prorenin. In contrast, renin and prorenin were clearly present in extracts of reproductive tissues. Ovarian total renin was lowest during anestrus (169 +/- 27 ng/g per h) and estrus (258 +/- 58 ng/g per h) and increased with ovulation (385 +/- 31 ng/g per h). Higher ovarian levels were found during pseudopregnancy (1370-2030 ng/g per h) and early pregnancy (1312-2700 ng/g per h) and in the placental chorion disc of early pregnancy (1755-1184 ng/g per h). In the uterus, the level was 98-183 ng/g per h during gestation. These results demonstrate that, in marked contrast to humans, only the cat kidney secretes prorenin into body fluids. Nonetheless, total renin increases in cat ovaries during follicle maturation, ovulation, pregnancy and pseudopregnancy, in the uterus during gestation and in the placental chorion disc. These results are consistent with an autocrine or paracrine role for the tissue renin system in cat reproductive tissues.

Amniotic Fluid↗

PubMed1991

Activation and function of prorenin: different viewpoints.

This Symposium includes 15 presentations and an editorial review dealing with prorenin activation and function. It comes 20 years after prorenin was first reported in various contexts and attracted attention because of its connection with renin--angiotensin, its high concentration relative to renin in the blood, and its presence in extrarenal, as well as renal, tissues. Intriguing changes in plasma prorenin have been reported after treatment with antihypertensive and other drugs, following various physiological stimuli, and in pathophysiological states such as Wilms' tumor, Bartter's syndrome, and diabetic nephropathy. Lately, very high prorenin concentrations have been found in human and animal ocular fluid, ovarian follicular fluid, and in association with angiogenesis and microangiopathy. High circulating prorenin concentrations and fulminant hypertension have been reported in rats harbouring the mouse Ren-2 gene. However, what prorenin does in all these extrarenal fluids, tissues, and conditions is not well understood. Among the reasons for this lack of understanding are the difficulties in measuring prorenin and in establishing good animal models. We have not answered the critical question as to whether prorenin itself is bioactive like a hormone, and if so, what its action(s) might be. Nor have we established the main alternative, i.e., whether the function of prorenin is indirect, through renin--angiotensin, be it in the circulation or in the extrarenal tissues. This Symposium provides only partial methodological advances and answers, but we hope it will stimulate the breakthrough work needed to supply more complete answers.

Enzyme Activation↗

PubMed1991

Trypsin activation of human and cat prorenin: a comparative study.

Prorenin can be converted to renin by limited proteolysis with trypsin. In the current study we compared conditions for activation of human renal and ovarian prorenin and cat renal prorenin with either liquid-phase trypsin or trypsin bound to sepharose (solid phase). Higher concentrations of trypsin were required to activate cat prorenin than human prorenin. Human prorenin was destroyed by high concentrations of trypsin, while cat prorenin was not destroyed by up to 2 mg/mL solid-phase trypsin. For both human and cat prorenin, addition of the competitive serine protease inhibitor benzamidine--HCl increased the concentration of trypsin needed to activate prorenin, resulting in slightly higher levels of human prorenin but lower levels of cat prorenin. For human samples, activation with solid-phase trypsin resulted in slightly higher estimates of prorenin than liquid-phase trypsin. These results demonstrate species differences in the susceptibility of prorenin to trypsin cleavage. Cat prorenin requires more trypsin to be activated and is less susceptible to destruction than human prorenin.

Animals↗

PubMed1991

Prorenin secretion from human placenta perfused in vitro.

We examined whether renin (prorenin plus renin) is secreted from the human placenta into the maternal or fetal circulation and compared the secretion rate to that of human chorionic gonadotropin (hCG), progesterone, and estradiol. While estradiol and progesterone passed into both circulations, renin (mostly prorenin) and hCG were secreted predominantly into the maternal circulation. To examine if prorenin passed from the maternal to the fetal circulation and vice versa, we perfused both circuits separately with exogenous recombinant human prorenin. No prorenin passed from maternal to fetal circulations, but a small amount (less than 10%) slowly passed from fetal to maternal, beginning 15 min after the addition of prorenin. Exogenous prorenin was not converted to renin in either circulation. Perfusate total renin had close to 10% active renin, whereas that of tissue extracts was closer to 50%. In conclusion, the results are consistent with some tissue activation of prorenin, either in vitro or in vivo, but no activation in the maternal or fetal circulations. The human placenta may secrete prorenin into the maternal but not into the fetal circulation. The possibility that the placenta may secrete a small amount of active renin into the maternal circulation was not ruled out.

Angiotensin II↗

PubMed1991

Half-life, hemodynamic, renal, and hormonal effects of prorenin in cynomolgus monkeys.

Prorenin is found in human plasma, kidneys, and reproductive organs. We investigated the physiological and pharmacokinetic properties of plasma prorenin, and its plasma conversion to active renin, by bolus infusions of human recombinant prorenin (0.5, 2, 20 micrograms; n = 4/dose) into anesthetized male cynomolgus monkeys. The infused prorenin had 3% intrinsic renin activity. Plasma prorenin rose from 61 +/- 6 to 101 +/- 11, 570 +/- 46, and 7,700 +/- 390 ng.ml-1.h-1, respectively, after 5 min. Plasma renin increased to 3% of total renin, angiotensin II increased less than twofold, and aldosterone did not change. Plasma testosterone fell slightly (P less than 0.01). Mean arterial pressure (MAP) fell slowly from 104 +/- 3 to 93 +/- 3 mmHg at 60 min (P less than 0.001). Heart rate, glomerular filtration rate, renal plasma flow, and urinary sodium and potassium excretion were unchanged. For the 2- and 20-micrograms doses, respectively, effective half-life of plasma decay was 47 +/- 4.9 and 109 +/- 21 min (P less than 0.05), apparent volume of distribution was 145 +/- 11 and 166 +/- 35 ml/kg, and metabolic clearance rate was 2.30 +/- 0.44 and 1.08 +/- 0.14 ml.min-1.kg-1 (P less than 0.01). In conclusion, neither the hormonal nor the physiological response to infusion of pharmacologic levels of recombinant human prorenin into monkeys provide evidence for conversion of circulating prorenin to renin. MAP did not increase and actually fell without commensurate effects on renal function. The half-life of recombinant prorenin was similar to that of renin.

Aldosterone↗

PubMed1991

Relationship of follicular fluid prorenin to oocyte maturation, steroid levels, and outcome of in vitro fertilization.

Prorenin (PR) is present in high concentrations in the follicular fluid (FF) of the preovulatory follicle. It is the predominant form of renin detected in FF. Its biosynthesis and secretion from the ovary are regulated by gonadotropins. In the present study we measured PR and steroid levels in FF from 136 follicles. Follicular fluids were obtained, 36 h after hCG injection, from 41 ovarian-stimulated patients who underwent follicle puncture and oocyte retrieval for in vitro fertilization. We related FF PR to steroid levels and to the stage of oocyte-cumulus complex maturation. PR levels in 62 FF containing mature healthy fertilized oocytes averaged 2620 +/- 157 (+/- SE) ng/mL.h (728 +/- 44 ng/L.s; range, 1020-6880 ng/mL.h, 283-1911 ng/L.s). A subgroup of 16 of these follicles containing mature oocytes were from 7 women who conceived, in which PR levels spanned only the lower range from 1030-2720 ng/mL.h (286-756 ng/L.s). No patient conceived with FF PR above 2800 ng/mL.h (778 ng/L.s), yet one third of all mature follicles were above this range. Lower levels of PR were detected in FF containing immature oocytes (germinal vesicle stage) associated with either compact (1665 +/- 480 ng/mL.h; 463 +/- 133 ng/L.s; n = 22; P less than 0.02) or expanded (1785 +/- 193 ng/mL.h; 496 +/- 54 ng/L.s; n = 24; P less than 0.005) cumulus mass; a subgroup (n = 5) of follicles with immature oocytes and compact cumulus had very high levels of FF PR, ranging from 3830-7520 ng/mL.h (1064-2089 ng/L.s), while the remainder had levels less than 1300 ng/mL.h (361 ng/L.s). Progesterone and estradiol (E2) were lower in FF surrounding immature oocytes associated with compact (P less than 0.005) or expanded (P less than 0.02) cumulus, than in those containing mature oocytes. Testosterone (T) and androstenedione were measured in only a fraction of the samples; there were no apparent differences between follicles containing mature and immature oocytes. However, T and androstenedione levels were high in the subgroup of follicles containing immature oocytes and very high levels of PR. Of the hormones measured, T revealed the most striking relationship with PR (r = 0.62; n = 49; P less than 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)

Androstenedione↗

PubMed1991

Comparison of transdermal to oral estradiol administration on hormonal and hepatic parameters in women with premature ovarian failure.

Five women with premature ovarian failure were studied in a randomized cross-over design to compare the biochemical effects of transdermal to oral estradiol administration when used in doses appropriate for endometrial preparation in a donor oocyte program. Patients randomly received increasing dosages of oral micronized or transdermal estradiol for 4 week, with progesterone added in the last 2 weeks, to mimic a normal hormonal cycle. Serum samples were assayed throughout treatment and compared to those from normally cycling premenopausal controls. In general, serum estradiol remained within the normal range in both treatment groups, whereas peak serum estrone levels were 10-fold higher in the orally treated group than those in the transdermally treated group. Serum levels of sex hormone-binding globulin, thyroid binding globulin, and renin substrate were all significantly elevated by day 14 in the orally treated patients and unchanged in the transdermal subjects. While plasminogen was unaltered by either route of administration, antithrombin-III levels fell with both treatments. Changes in gonadotropin levels were similar in both groups, with suppression of FSH by the end of the simulated cycles, but not into the normal premenopausal range. In conclusion, both estrogen replacement regimens provided near-normal serum estradiol profiles. However, despite the relatively high doses necessary to mimic a hormonally normal cycle, the transdermal route did not significantly alter the hepatic parameters studied, suggesting that this route of administration may have less adverse hepatic effects.

Administration, Cutaneous↗

PubMed1991

Plasma renin activity and plasma prorenin assays.

Sensitivity and accuracy are essential features of an assay of plasma renin activity (PRA) because the normal concentration of PRA is only 1 pmol/L, and subnormal concentrations have diagnostic relevance. Conditions for blood collection need to be standardized but the conditions are not difficult for outpatients. For routine diagnostic purposes blood should be collected from ambulatory (ideally, untreated) patients on moderate sodium intake. To avoid irreversible cryoactivation of plasma prorenin (which is present in 10-fold greater concentrations than renin), samples should be processed at room temperature and stored completely frozen. Cryoactivation occurs when plasma is liquid at temperatures less than 6 degrees C. PRA is commonly measured with an enzyme kinetic assay in which angiotensin I (Ang I) is formed by the reaction of plasma renin with endogenous renin substrate (angiotensinogen). The Ang I so formed is measured by RIA; results are expressed as an hourly rate (micrograms/L formed per hour). This method, which is provided by most commercial kits, has the potential for unlimited sensitivity because the step for Ang I generation can be prolonged as long as necessary, so that enough Ang I forms to be measured accurately. Unfortunately, that sensitivity is not always exploited. Dilution of plasma during pH adjustment should be kept to a minimum. The Ang I generation step should last at least 3 h. The step should last 18 h for samples with PRA less than 1.0 micrograms/L per hour, to eliminate the errors inherent in the measurement and subtraction of immunoreactive Ang I in the untreated plasma (blank subtraction). These changes actually simplify PRA measurements because they eliminate the need for ice in the clinic and reduce by almost half the number of samples to be assayed by RIA. I also describe the method for measurement of plasma prorenin, which may be an important marker for patients with diabetes mellitus who subsequently develop vascular complications.

Angiotensin I↗

PubMed1991

Abnormal sodium metabolism and plasma renin activity (renal renin secretion) and the vasoconstriction volume hypothesis: implications for pathogenesis and treatment of hypertension and its vascular consequences (heart attack, stroke).

Arterial hypertension is sustained by either of two long-term mechanisms of arteriolar vasoconstriction or by an inappropriate reaction between them. One mechanism is renin-mediated, the other is related to antecedent renal sodium retention. The plasma renin value directly reflects the presence and degree of renin-mediated vasoconstriction, and, inversely, defines the predominance of sodium-related vasoconstriction. A hypotensive response, or lack of it, to angiotensin-converting enzyme inhibitor is similarly informative. Because the normal kidney exposed to high arterial pressure and normal salt intake will reduce its renin secretion to near zero, any renin secretion in a hypertensive setting can be considered abnormal. Typically, high-renin hypertensive patients are more vasoconstricted than low-renin patients with similar blood pressures. The intense vasoconstriction leads to relative hypovolemia, hemoconcentration, hyperviscosity, postural hypotension, and in severe forms even to acrocyanosis, all of which are dramatically reversed with anti-renin therapy. Conversely, low-renin equally hypertensive patients have relatively more sodium volume and are less vasoconstricted; they are generally responsive to natriuretic drugs (e.g., diuretics or calcium antagonists) and appear relatively protected from vascular sequelae such as stroke and heart attack. These observations provide a new means for evaluating prognosis and a basis for mechanistically differentiating and treating hypertensive patients, allowing increasingly simpler and more-specific long-term therapies.

Animals↗

PubMed1990

Longitudinal study of the renin-angiotensin-aldosterone system in hypertensive pregnant women: deviations related to the development of superimposed preeclampsia.

A prospective longitudinal study of 25 pregnant women (30 pregnancies) with chronic hypertension, a group prone to development of preeclampsia, was conducted to explore the relationship between the renin-angiotensin-aldosterone system and the development of superimposed preeclampsia. In women with chronic hypertension in whom preeclampsia did not develop (17 pregnancies), blood pressure decreased and the renin-angiotensin-aldosterone system was stimulated, beginning in the first trimester and continuing throughout pregnancy as found previously in normotensive pregnant women (n = 58). Plasma estradiol and progesterone levels also increased progressively. In women with chronic hypertension in whom preeclampsia developed (13 pregnancies), blood pressure decreased and the renin-angiotensin-aldosterone system was stimulated in the first trimester as in the other groups. However, later in pregnancy significant differences were observed. Blood pressure began to rise in the second trimester. Initially the renin-angiotensin-aldosterone system remained stimulated, but in the early third trimester, when preeclampsia was diagnosed, plasma renin activity and urine aldosterone excretion decreased, and atrial natriuretic factor increased. These data provide information that may be useful in the recognition of superimposed preeclampsia, and in the investigation of its pathogenesis.

Adult↗

PubMed1990

Diurnal and postural variations in plasma atrial natriuretic factor, plasma guanosine 3':5'-cyclic monophosphate and sodium excretion.

1. We studied diurnal patterns of plasma atrial natriuretic factor, plasma guanosine 3':5'-cyclic monophosphate and urinary sodium excretion in normal subjects after 3 days on a 200 mmol of sodium/60 mmol of potassium diet. On the fourth day blood samples and urine were collected every 3 h. 2. Two studies were performed. In study 1, normal subjects (n = 8) were recumbent for 23 h from 09.00 hours to 08.00 hours the next day. In study 2, normal subjects (n = 10) were permitted to ambulate from 09.00 hours to 23.00 hours and then were recumbent until 08.00 hours the next day. 3. In study 1, assumption of the recumbent posture was associated with increases in plasma atrial natriuretic factor (P less than 0.01), plasma guanosine 3':5'-cyclic monophosphate (P less than 0.05) and urinary sodium excretion (P less than 0.05). 4. In contrast, in study 2 there were no significant changes in plasma atrial natriuretic factor during the day; instead, plasma atrial natriuretic factor increased overnight, reaching a peak at 24.00 hours after 1 h of recumbency (P less than 0.01). A smaller rise in plasma guanosine 3':5'-cyclic monophosphate (P less than 0.05) occurred; urinary sodium excretion decreased markedly (P less than 0.01) and there was no change in creatinine clearance. 5. In both studies, recumbency was associated with an initial drop, followed by a rise, in packed cell volume. 6. These data demonstrate that assumption of the supine position induces a rise in plasma atrial natriuretic factor and accounts for most of the observed variation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗