Subsequent Development Of Hypertension Research Articles

Shock Wave Lithotripsy is Not Predictive of Hypertension Among Community Stone Formers at Long-Term Followup

Concern exists over the subsequent development of hypertension after shock wave lithotripsy for the treatment of symptomatic urolithiasis. Referral bias and lack of long-term followup have been limitations of prior studies. We identified all Olmsted County, Minnesota residents with a diagnosis of urolithiasis from 1985 to 2008. The charts were electronically queried for hypertension and obesity by diagnostic codes, and use of shock wave lithotripsy by surgical codes. All patients first diagnosed with hypertension before or up to 90 days after the first documented kidney stone were considered to have prevalent hypertension and were excluded from analysis. Cox proportional hazards models were used to assess the association of shock wave lithotripsy with a subsequent diagnosis of hypertension. We identified 6,077 patients with incident urolithiasis with more than 90 days of followup. We excluded 1,295 (21.3%) members of the population for prevalent hypertension leaving 4,782 patients with incident urolithiasis for analysis. During an average followup of 8.7 years new onset hypertension was diagnosed in 983 (20.6%) members of the cohort at a mean of 6.0 years from the index stone date. Only 400 (8.4%) patients in the cohort were treated with shock wave lithotripsy. There was no significant association between shock wave lithotripsy and the development of hypertension in univariate (p = 0.33) and multivariate modeling controlling for age, gender and obesity (HR 1.03; 95% CI 0.84, 1.27; p = 0.77). In a large population based cohort of kidney stone formers we failed to identify an association between shock wave lithotripsy and the subsequent long-term risk of hypertension.

Early glomerular alterations in genetically determined low nephron number

An association between low nephron number and subsequent development of hypertension in later life has been demonstrated. The underlying pathomechanisms are unknown, but glomerular and postglomerular changes have been discussed. We investigated whether such changes are already present in prehypertensive "glial cell line-derived neurotrophic growth factor" heterozygous mice (GDNF+/-) with lower nephron number. Twenty-six-week-old mice [22 GDNF+/-, 29 C57B6 wild-type control (wt)] were used for in vivo experiments with intra-arterial and tail cuff blood pressure measurements. After perfusion fixation, kidneys were investigated with morphological, morphometric, stereological, and immunohistochemical techniques and TaqMan PCR analysis. As expected at this age, blood pressure was comparable between GDNF+/- and wt. Nephron number per kidney was significantly lower in GDNF+/- than in wt (-32.8%, P < 0.005), and mean glomerular volume was significantly higher (+49.5%, P < 0.001). Renal damage scores, glomerular and tubular proliferation, analysis of intrarenal arteries and peritubular capillaries, expression of relevant tubular transporter proteins, as well as gene expression of profibrotic, proinflammatory, or prohypertensive markers were not significantly different between GDNF+/- and wt. Compensatory glomerular hypertrophy in GDNF+/- was accompanied by higher numbers of endothelial and mesangial cells as well as PCNA-positive glomerular cells, whereas podocyte density was significantly reduced. Further electron microscopic analysis showed marked thickening of glomerular basement membrane. In conclusion, lower nephron number is associated with marked early glomerular structural changes, in particular lower capillary supply, reduced podocyte density, and thickened glomerular basement membrane, that may predispose to glomerular sclerosis.

Vascular insulin resistance in prehypertensive rats: Role of PI3-kinase/Akt/eNOS signaling

It is well known that systemic insulin resistance is closely associated with the metabolic syndrome including type 2 diabetes and hypertension. However, it remains unclear whether vascular insulin resistance acts as an early etiologic factor for the development of hypertension. Male spontaneously hypertensive rats (SHRs) aged 5 weeks (young) and 15 weeks (adult) were studied and vascular insulin resistance was assessed as the function of isolated aortic vasodilatory response to insulin in vitro. Compared with Wistar–Kyoto (WKY) rats, adult SHRs exhibited significant hypertension with significantly decreased aortic vasodilatation to insulin, whereas young SHRs had normal blood pressure but exhibited similar vascular insulin resistance. Both young and adult SHRs showed significant downregulated expression of PI3-kinase and decreased insulin-stimulated phosphorylations of Akt and eNOS in vascular tissues. Treatment with rosiglitazone (RSG), an insulin sensitizer, for 2 weeks increased vascular PPARγ expression and restored PI3-kinase/Akt/eNOS-mediated signaling pathway only in young SHRs. More importantly, this treatment improved aortic vasodilatory response to insulin in young but not in adult SHRs. In summary, vascular insulin resistance, characterized by the impairment of PI3-kinase/Akt/eNOS-mediated signaling in vascular endothelium, may play important roles in endothelial dysfunction and subsequent development of hypertension in normotensive young SHRs.

Abstract 5535: Vascular Insulin Resistance in Prehypertensive Rats Contributes to the Development of Hypertension: Role of PI3 Kinase/Akt/Enos Signaling

Objective: It is well known that systemic insulin resistance (IR) is closely associated with metabolic syndrome including type 2 diabetes and hypertension. However, it remains unclear whether vascular IR acts as an early etiologic factor for the development of hypertension. The present study aimed to test the hypothesis that vascular IR in the conduit arteries contributes to the pathogenesis of hypertension in hypertension-prone normotensive rats, and to further investigate the underlying mechanism. Methods: Male spontaneously hypertensive rats (SHRs) aged 5-weeks (young) and 15-weeks (adult) were studied and vascular IR was assessed as the function of isolated aortic vasodilatory response to insulin in vitro . Results: Compared with Wistar-Kyoto (WKY) rats, adult SHRs exhibited significant hypertension (systolic blood pressure, 173±4 vs. 121±4 mmHg in adult WKY, n = 8, P &lt;0.01) with significantly decreased aortic vasodilatation to insulin (38.7±4.4% vs. 70.9±3.6%, n = 8 –10 aortic segments/group from 5–7 rats, P &lt;0.01), whereas young SHRs had normal blood pressure (121±2 vs. 114±4 mmHg in young WKY, P &gt;0.05) but exhibited similar vascular IR (42.3±5.2% vs. 68.5±5.9%, P &lt;0.01). Both young and adult SHRs showed significant downregulated expression of PI3-Kinase and decreased insulin-stimulated phosphorylations of Akt and eNOS in vascular tissues (n = 3, P &lt;0.01). More importantly, treatment with rosiglitazone (RSG), an insulin sensitizer, for 2 wks increased vascular PPAR γ expression and restored PI3-Kinase/Akt/eNOS-mediated signaling pathway induced by insulin, thus improved aortic vasodilatory response to insulin in young but not in adult SHRs ( P &lt;0.05). Conclusion: Vascular IR, characterized by the impairment of PI3-Kinase/Akt/eNOS signaling in vascular endothelium, may play a role in endothelial dysfunction and subsequent development of hypertension in normotensive young SHRs.

Aldosterone to Renin Ratio (ARR) in Clinical use, with Reference to the Primary Care Setting: ARR to Whom, When, How, What for?

Compelling evidence indicates that primary aldosteronism (PA) is the most frequent cause of secondary hypertension, with an estimated prevalence ranging from 10 to 15% in the population referred to specialist hypertension units. In clinical practice, the aldosterone to renin ratio (ARR) is the cornerstone of population screening, although difficulties in methodology and thus in defining precise cut-off values still represent an area of uncertainty. In hypertensive subjects, the elevated ARR is a marker of inappropriately high aldosterone secretion for the degree of renin-angiotensin system activation, and often is the only index capable of distinguish normokalemic PA from essential hypertension. On the basis of such a high prevalence, it is unclear whether ARR measurement should be reserved for selected subgroups of patients, or extended to all hypertensive subjects in the population as a whole. In unselected, normotensive populations elevated aldosterone levels and elevated ARR have recently been reported as predisposing factors to the subsequent development of hypertension, raising the question of the optimal timing for ARR measurement, especially in those with a family history of hypertension in primary care. In a large proportion of patients presenting elevated ARR the diagnosis of PA is formally ruled out by confirmatory/ exclusion testing, although the clinical relevance of “inappropriate aldosterone secretion” in these patients remains unclear. May it serve as a predictor of the usefulness of mineralocorticoid receptor antagonist treatment? These and related questions will be examined in this review, particularly given clearly unsatisfactory levels of BP control even in the populations of Western countries.

Mechanisms of lead-induced hypertension and cardiovascular disease

Lead is a ubiquitous environmental toxin that is capable of causing numerous acute and chronic illnesses. Population studies have demonstrated a link between lead exposure and subsequent development of hypertension (HTN) and cardiovascular disease. In vivo and in vitro studies have shown that chronic lead exposure causes HTN and cardiovascular disease by promoting oxidative stress, limiting nitric oxide availability, impairing nitric oxide signaling, augmenting adrenergic activity, increasing endothelin production, altering the renin-angiotensin system, raising vasoconstrictor prostaglandins, lowering vasodilator prostaglandins, promoting inflammation, disturbing vascular smooth muscle Ca(2+) signaling, diminishing endothelium-dependent vasorelaxation, and modifying the vascular response to vasoactive agonists. Moreover, lead has been shown to cause endothelial injury, impede endothelial repair, inhibit angiogenesis, reduce endothelial cell growth, suppress proteoglycan production, stimulate vascular smooth muscle cell proliferation and phenotypic transformation, reduce tissue plasminogen activator, and raise plasminogen activator inhibitor-1 production. Via these and other actions, lead exposure causes HTN and promotes arteriosclerosis, atherosclerosis, thrombosis, and cardiovascular disease. In conclusion, studies performed in experimental animals, isolated tissues, and cultured cells have provided compelling evidence that chronic exposure to low levels of lead can cause HTN, endothelial injury/dysfunction, arteriosclerosis, and cardiovascular disease. More importantly, these studies have elucidated the cellular and molecular mechanisms of lead's action on cardiovascular/renal systems, a task that is impossible to accomplish using clinical and epidemiological investigations alone.

Diagnostic and Therapeutic Approach to Nonsleepy Apnea

Epidemiological and observational studies suggest that sleep-disordered breathing is associated with the subsequent development of hypertension and ultimately with cardiovascular consequences. It may therefore be assumed that continuous positive airway pressure (CPAP) not only avoids sleep-related symptoms but could also mitigate cardiovascular consequences. Short-term studies have revealed a drop in blood pressure, especially in more severe, symptomatic cases of obstructive sleep apnea. Two recent studies have reported that nonsleepy obstructive sleep apnea is associated with an absence of reduced blood pressure after CPAP treatment. This suggests that this group of patients is less susceptible to the consequences of apneas, even those with mild-moderate hypertension or other cardiovascular disorders. However, in patients with severe cardiovascular disease or a higher number of obstructive events, CPAP treatment should be seriously considered.

Fetal programming of hypertension

Numerous epidemiological studies suggest an inverse relationship between low birth weight (LBW) and hypertension, an observation now supported by numerous animal studies. The mechanisms linking LBW and hypertension appear to be multifactorial and involve alterations in the normal regulatory systems and renal functions involved in the long-term control of arterial pressure. Recent studies using animal models of fetal programming suggest that programming during fetal life occurs in response to an adverse fetal environment and results in permanent adaptive responses that lead to structural and physiological alterations and the subsequent development of hypertension. This review summarizes the adaptive responses observed in the different models used to induce a suboptimal fetal environment and discusses insights into the mechanisms mediating the fetal programming of hypertension.

A Prospective Study of Plasma Lipid Levels and Hypertension in Women

Although dyslipidemia and hypertension occur together more often than can be explained by chance, few studies have carefully explored the nature of the relationship between plasma lipid levels and the risk of developing hypertension. We conducted a prospective study of 16 130 middle-aged and older female health professionals in 1992 who provided baseline blood samples and had no history of high cholesterol level (no treatment or diagnosis) or hypertension (no treatment, diagnosis, or elevated blood pressure). Plasma lipid levels were measured, and baseline risk factors were collected. Incident hypertension included a new physician diagnosis, the initiation of antihypertensive treatment, systolic blood pressure of 140 mm Hg or greater, or diastolic blood pressure of 90 mm Hg or greater. During 10.8 years of follow-up, incident hypertension developed in 4593 women. In multivariate-adjusted models, the relative risks of development of hypertension from the lowest (referent) to the highest quintile of baseline total cholesterol level were 1.00, 0.96, 1.02, 1.09, and 1.12 (P = .002 for trend); for low-density lipoprotein cholesterol level, 1.00, 0.97, 1.00, 1.02, and 1.11 (P = .053 for trend); for high-density lipoprotein cholesterol level, 1.00, 0.93, 0.87, 0.87, and 0.81 (P < .001 for trend); for non-high-density lipoprotein cholesterol level, 1.00, 1.06, 1.11, 1.12, and 1.25 (P < .001 for trend); and for the ratio of total to high-density cholesterol, 1.00, 1.10, 1.14, 1.20, and 1.34 (P < .001 for trend). Similar relative risks were noted for Adult Treatment Panel III clinical cut points and after the exclusion of obese or diabetic women. In this large prospective cohort, atherogenic dyslipidemias were associated with the subsequent development of hypertension among healthy women.

1847 The incidence rate and the determinants of subsequent development of hypertension in normotensive screened subjects in Okinawa, Japan

1847 The incidence rate and the determinants of subsequent development of hypertension in normotensive screened subjects in Okinawa, Japan

Hypertension in renal transplantation: donor and recipient risk factors.

To determine the respective roles of donor and recipient factors in the subsequent development of hypertension after renal transplantation. All the patients transplanted between January 1990 and December 1999 who still had a functioning graft 1 year post-transplant (n = 321) were retrospectively studied. Blood pressure was assessed at 1 year post-transplant. Hypertension was defined as a systolic BP > or equal 140 mmHg or diastolic BP > or equal 90 mmHg, or use of antihypertensive medication. Relevant donor and recipient characteristics were recorded. Two-hundred-and-sixty-three patients (82%) were hypertensive. In multivariate analysis, pretransplant hypertension (RR, 1.74, 95% CI, 1.07 to 2.87), anticalcineurin use (RR, 2.59, 95% CI, 1.13 to 5.92), urinary protein excretion (RR, 1.84, 95% CI, 1.06 to 3.18), BMI (RR, 1.08, 95% CI, 1.01 to 1.16), donor age (RR, 1.28,95% CI, 1.05 to 1.59, for each 10-year increase in donor age) and donor aortorenal atheroma (OR, 2.34; 95% CI, 1.24 to 4.46) were associated with hypertension. Among patients under calcineurin inhibitors, those receiving cyclosporine were more prone to have hypertension than those receiving tacrolimus (88.7% vs 78%; p = 0.04). Both recipient and donor factors contribute to hypertension in RTR.

Vesicoureteral reflux and evidence-based management

Vesicoureteral reflux and evidence-based management

Relative glucose tolerance and subsequent development of hypertension in pregnancy

Objective: To test the hypothesis that relative carbohydrate tolerance, an indicator of insulin resistance, predicts subsequent risk for hypertension of pregnancy among previously normoglycemic, normotensive women. Methods: We conducted a nested case-control study in women enrolled at a large Colorado urban health maintenance organization. Subjects were previously healthy pregnant women who tested abnormal on their initial 50-g glucose screens and subsequently completed 3-hour, 100-g oral glucose tolerance tests. Cases were 54 previously normotensive women who subsequently developed hypertension and controls were 51 subjects with normotensive pregnancies, matched to cases on parity. Subjects diagnosed with gestational diabetes (17 cases, six controls) were excluded from the main analyses. Results: Among the 82 normoglycemic women (45 controls, 37 cases, 13 preeclampsia, 24 gestational hypertension), mean post-load glucose levels and total glucose area under the curve were significantly higher in cases than in controls ( P ≤ .04) and were positively correlated with peak mean arterial pressure. After adjustment for potential confounders, 2-hour post-load glucose levels remained strongly related to risk for hypertension (adjusted odds ratios = 1.48; 95% confidence interval 1.13, 1.92, per 10 mg/dL increase) and to peak mean arterial blood pressure ( r = .23, P = .04), as did total glucose area under the curve ( P ≤ .04). Cases were also more likely to have had one abnormal glucose tolerance test (28% versus 5%, P = .004). Stratifying analyses by case severity (preeclampsia and gestational hypertension) yielded similar results. Among all subjects, more cases than controls were also diagnosed with gestational diabetes (31% versus 12%, P = .008). Conclusion: These findings are consistent with the hypothesis that insulin resistance precedes the clinical onset of hypertension in pregnancy, and may be important in the etiology of hypertension.

The value of elevated second-trimester β-human chorionic gonadotropin in predicting development of preeclampsia

OBJECTIVE: Our purpose was to investigate the association of an elevated second-trimester serum β-human chorionic gonadotropin concentration with the subsequent development of hypertension in pregnancy and to evaluate its utility as a screening test for preeclampsia. STUDY DESIGN: We examined 6286 nondiabetic women with singleton pregnancies who, as part of triple-screen testing, had a serum β human chorionic gonadotropin level drawn between 15 and 22 weeks' gestation between November 1, 1991, and November 30, 1994. Medical records of women with hypertension ( n = 675) were reviewed, patients with chronic hypertension were excluded, and the remainder were classified as having gestational hypertension ( n = 333), mild preeclampsia ( n = 110), or severe preeclampsia ( n = 84). The β-human chorionic gonadotropin level expressed as multiples of the median adjusted for maternal weight and gestational age was compared between normotensive and hypertensive complicated pregnancies. RESULTS: In the overall population β-human chorionic gonadotropin levels ≥2.0 multiples of the median during the second trimester were significantly associated with development of hypertension in pregnancy. The rate ratio for development of overall hypertension was 1.6 (95% confidence interval 1.3 to 2.0) and for preeclampsia 1.8 (95% confidence interval 1.3 to 2.6). When stratified by parity, a statistically significant association remained only among multiparous women, for overall hypertension (rate ratio 2.2, 95% confidence interval 1.6 to 3.2) and for preeclampsia (rate ratio 3.4, 95% confidence interval 2.1 to 5.6). Adjusting for confounding factors did not alter the results. In the overall population, with the use of 2.0 multiples of the median of β-human chorionic gonadotropin as a cutoff value, the sensitivity of β-human chorionic gonadotropin as a screen for development of hypertension was 15.6%, the specificity was 90.0%, and the positive predictive value was 12.8%. CONCLUSION: Overall, second-trimester serum β-human chorionic gonadotropin levels were elevated among women who had hypertension during pregnancy. In our population this association was statistically significant only among multiparous women. The utility of an elevated second-trimester β-human chorionic gonadotropin level as a screening test for preeclampsia is limited.(Am J Obstet Gynecol 1997;176:438-42.)

Conscious obese rats have impaired reflex bradycardia and enhanced norepinephrine sensitivity.

Male Sprague-Dawley rats fed a condensed milk diet were classified as either "obesity susceptible" (OS) or "obesity resistant" (OR) based on body weight increases attained after 12 wk. Overall caloric intake in OS rats was higher than in chow-fed controls, and OS rats were heavier than chow-fed controls or OR rats. There were no significant differences in blood glucose, serum insulin, ventricular weight, basal blood pressure, or heart rate. Pressor responses recorded after combined blockade with atropine and propranolol to eliminate reflex effects were identical for vasopressin, but those to norepinephrine were larger in OS than in OR rats, whereas those to angiotensin were larger in OS than in control rats. When baroreflex sensitivity was assessed using intravenously infused sodium nitroprusside or phenylephrine to alter systemic arterial pressure, differences in reflex tachycardia were equivocal, but reflex bradycardia was clearly inhibited in OS rats. These results show that, although basal blood pressure was unaffected in OS rats, their impaired reflex bradycardia along with enhanced pressor responsiveness to norepinephrine could predispose them to subsequent development of hypertension.

Type 2 11 beta-hydroxysteroid dehydrogenase messenger ribonucleic acid and activity in human placenta and fetal membranes: its relationship to birth weight and putative role in fetal adrenal steroidogenesis.

Two isoforms of 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) have been described which catalyze the interconversion of cortisol (F) to cortisone (E). 11 beta HSD activity has previously been reported in placenta and fetal membranes, where its role may be to protect the developing fetus from glucocorticoid excess. Furthermore, in the rat, an association between placental 11 beta HSD activity and the subsequent development of hypertension in the offspring has been reported. We have characterized the isoforms of 11 beta HSD in human fetal membranes and dissected placental tissue at term and investigated the relationship between placental 11 beta HSD activity and fetal and placental weights. 11 beta HSD activity studies in the presence of 0.1 mumol/L F and NAD (indicative of type 2 isoform activity) revealed high levels of activity in trophoblast dissected free of vessels (561 +/- 87 pmol E/h.mg protein; n = 4) > undissected placenta > cotyledenous vessels dissected away from trophoblast > placental and reflected amnion. In contrast, in the presence of 2.5 mumol/L F and NADP (indicative of type 1 isoform activity), only decidua and chorion demonstrated significant levels of 11 beta HSD activity. Type 1 11 beta HSD activity in chorion was probably due to decidual contamination, in that it was absent in decidua-free fused chorion obtained from a twin pregnancy. In keeping with these data, type 1 11 beta HSD messenger ribonucleic acid (1.5 kilobases) was detected in decidua, but in no other tissue, and high levels of type 2 11 beta HSD messenger ribonucleic acid (1.9 kilobases) were found in undissected placenta and trophoblast. In 27 term placentas, 11 beta HSD activity varied from 194-448 pmol E/h.mg protein. There was a weak, but significant, positive correlation between term placental 11 beta HSD activity and fetal weight (r = 0.408; P = 0.034), but no correlation with placental weight. Thus, in man, the reported association of a small fetus and a large placenta predisposing to adult hypertension cannot be explained on the basis of defective 11 beta HSD activity. However, the placenta offers an immense reservoir for F clearance (1.73-7.95 mumol/min.placenta) and may be a principal factor driving fetal ACTH secretion and, hence, fetal adrenal steroidogenesis.

Racial Differences in Renal Sodium Excretion: Relationship to Hypertension

Black Americans are more susceptible to hypertension and to renal disease than white Americans. Both normotensive and hypertensive blacks are more apt to have salt-sensitive blood pressure responses to the challenge of a salt load than whites. Moreover, salt sensitivity of blood pressure in both normotensive and hypertensive subjects is associated with a decreased excretory capacity for sodium, implicating the kidney in this phenomenon. Salt sensitivity of blood pressure also is associated with increasing age and, in normotensive subjects, may predict the subsequent development of hypertension. Radical differences in a variety of humoral as well as hemodynamic responses to physical and mental stressors have been identified. The relationships between these observations and renal sodium handling require further investigation.

Salt Sensitivity as a Predictor of Hypertension

Salt sensitivity of blood pressure can be identified in half of the hypertensive population and one-fourth of normotensive subjects. Salt sensitivity of blood pressure is especially frequent in normotensives from subpopulations known to have a higher frequency of hypertension, such as blacks, older subjects, and first-degree relatives of hypertensives, suggesting a link between salt and the subsequent development of hypertension. A variety of associated markers of salt sensitivity has been described. Recent studies also link calcium and salt sensitivity of blood pressure.

Age-Dependent Salt-Induced Hypertension in the Rat: Prevention with DSP-4, A Selective Noradrenergic Neurotoxin

The present study was performed to determine if chronic administration of a high salt diet induces hypertension similarly in young and adult rats and if treatment with DSP-4 alters the development of the hypertension. Three- (young) and ten- (adult) week-old male Sprague-Dawley rats were fed either a standard rat chow diet (0.71% NaCl), a 4% NaCl diet or an 8% NaCl diet for 12 weeks. Systolic blood pressure, using a standard tail-cuff technique, and body weight were recorded weekly during the dietary treatment period. Direct mean arterial pressure, heart rate, heart weight and kidney weight were determined after 12 weeks. Body weight was slightly reduced in young rats on the 8% NaCl diet. A significant increase in blood pressure as well as heart weight was observed only in young rats on the 8% NaCl diet. An increase in kidney weight was observed in both young and adult rats on the 8% NaCl diet. DSP-4 treatment prevented the development of hypertension as well as cardiac hypertrophy in rats fed the high salt diet but had no effect on rats receiving the normal diet. Body and kidney weights were similar in vehicle- and DSP-4-treated rats on the 8% NaCl diet. These results demonstrate that a critical developmental/maturational period exists during which the young rat is susceptible to the hypertensinogenic effects of a high salt diet. An intact central noradrenergic system appears to be necessary for the expression of this enhanced susceptibility and the subsequent development of hypertension.

Change in plasma cystyl aminopeptidase (oxytocinase) between 30-34 weeks' gestation as a predictor of pregnancy-induced hypertension.

Ninety-two primigravidas were screened biweekly by measurement of plasma cystyl aminopeptidase from 28 weeks' gestation until delivery. Fourteen developed hypertension with or without proteinuria after 36 weeks. The hypertensive group had significantly higher levels of the enzyme at 30 weeks, although this difference was not significant at 34 weeks. The rise in the hypertensive group was less than 50% between weeks 30-34 in all cases, whereas it was over 50% in all but two of the 43 controls. The difference in the rates of increase of the enzyme and its action on antidiuretic hormone may have some bearing on the subsequent development of hypertension.