Possible role of increased blood viscosity in the hemodynamics of systemic hypertension.
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Adult↗
Biomedical subjects
J H Laragh
Publications and source records attributed to J H Laragh.
Beta-adrenergic receptor blockade as a therapeutic approach for suppressing the renin-angiotensin-aldosterone system in normotensive and hypertensive subjects.
Although beta-adrenergic-blocking drugs suppress the renin system (RAAS), plasma angiotensin II (Ang II) responses during beta-blockade have not been defined. This study quantifies the effects of beta-blockade on the RAAS and examines its impact on prorenin processing by measuring changes in the ratio of plasma renin activity (PRA) to total renin. In normotensive (N = 14) and hypertensive (N = 16) subjects, blood pressure (BP), heart rate, PRA, plasma prorenin, plasma total renin (prorenin + PRA), ratio of PRA to total renin (%PRA), plasma Ang II, and urinary aldosterone were measured before and after 1 week of beta-blockade. Plasma renin activity, Ang II, and urinary aldosterone levels were similar for normotensive and hypertensive subjects. Plasma renin activity correlated with Ang II. Total renin, which is proportional to (pro)renin gene expression, was lower in hypertensive subjects and was inversely related to BP. Beta-blockade decreased BP and heart rate in both groups, with medium- and high-renin hypertensive subjects responding more frequently than those with low renin. Beta-blockade consistently suppressed PRA, Ang II, and aldosterone. Total renin was unchanged, thus, %PRA fell. These results indicate that beta-blockers suppress plasma angiotensin II levels, in parallel with the marked reductions in PRA and urinary aldosterone levels in normotensive and hypertensive subjects. The suppression of Ang II levels was comparable to that produced during angiotensin converting enzyme (ACE) inhibition. However, by reducing prorenin processing to renin, beta-blockers do not stimulate renin secretion, unlike ACE inhibitors and Ang II receptor antagonists. This unique action of beta-blockers has important implications for the treatment of cardiovascular disease.
Adrenergic beta-Antagonists↗
Delayed recovery of hypertension after single dose losartan in angiotensin II-infused conscious rats.
OBJECTIVE: In a conscious unrestrained rat model, it takes approximately 1 week for angiotensin II to increase blood pressure to maximum levels. We investigated the time required for hypertension to fully recover after acute angiotensin II receptor blockade in this angiotensin II dependent hypertensive model. DESIGN: Conscious unrestrained rats (n = 8) infused with 10 ng/kg per min angiotensin II for 21 days received losartan (10 mg/kg) on day 17 of angiotensin II infusion. Mean arterial pressure (MAP) and heart rate were monitored continuously. The acute pressor response to 50 ng/kg per min angiotensin II was monitored for 2 h on days 15, 17, 18, 19 and 20 of angiotensin II infusion. Plasma renin concentration (PRC) was measured daily. RESULTS: Angiotensin II increased MAP acutely by 26 +/- 2 mmHg and by a further 23 +/- 4 mmHg between days 4 and 8. Losartan acutely reduced MAP by 75 +/- 2 mmHg; 24 h later MAP had partially recovered but remained suppressed by 47 +/- 3 mmHg. MAP had not fully recovered 4 days later. Some 2 h after losartan, the acute pressor response to angiotensin II had fallen from 24 +/- 2 mmHg to zero. This recovered to 13 +/- 5 and 28 +/- 2 mmHg 24 and 48 h post losartan. After losartan PRC rose from 0.1 +/- 0.05 to above 1 ng/ml per h for less than 24 h. CONCLUSION: A single dose of losartan reverses both the fast and slow pressor effects of continuous angiotensin II infusions. While losartan is metabolized, the fast vasoconstrictor effect recovers quickly but the slow pressor effect takes almost a week to build up again to maximum levels. Since the slow pressor effect is mediated via the AT1 receptor, any means of blocking the renin-angiotensin system is likely to keep blood pressure below maximum hypertensive levels for several days after the drug has disappeared from the circulation.
Angiotensin II↗
Appropriate regulation of renin and blood pressure in 45-kb human renin/human angiotensinogen transgenic mice.
The renin-angiotensin system is normally subject to servo control mechanisms that suppress plasma renin levels in response to increased blood pressure and increase plasma renin levels when blood pressure falls. In most species, renin is rate limiting, and angiotensinogen circulates at a concentration close to the Km, so varying the concentration of either can affect the rate of angiotensin formation. However, only the plasma renin level responds to changes in blood pressure and sodium balance to maintain blood pressure homeostasis. Therefore, the high plasma human renin levels and the hypertension of mice and rats containing both human renin and angiotensinogen transgenes indicate inappropriate regulation of renin and blood pressure. These anomalies led us to develop new lines of transgenic mice with a longer human renin gene fragment (45 kb) than earlier lines (13 to 15 kb). Unlike their predecessors, the 45-kb hREN mice secrete human renin only from the kidneys, and both the human and mouse renins respond appropriately to physiological stimuli. To determine whether blood pressure is also regulated appropriately, we crossed these new 45-kb hREN mice with mice containing the human angiotensinogen gene. All doubly transgenic mice were normotensive like their singly transgenic and nontransgenic littermates. Moreover, among doubly transgenic mice, both human and mouse plasma renin concentrations were suppressed relative to the singly transgenic 45-kb hREN mice. These findings demonstrate the importance of appropriate cell and tissue specificity of gene expression in constructing transgenic models and affirm the pivotal role played by renal renin secretion in blood pressure control.
Aging↗
Renin system analysis: a rational method for the diagnosis and treatment of the individual patient with hypertension.
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Antihypertensive Agents↗
Renin system analysis defines the special value of combination antihypertensive therapy using an antirenin agent (CEI) with a long-acting calcium channel blocker (CCB).
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Angiotensin-Converting Enzyme Inhibitors↗
Identical hemodynamic and hormonal responses to 14-day infusions of renin or angiotensin II in conscious rats.
OBJECTIVE: To investigate whether plasma angiotensin II (Ang II) determines the effects of the renin-angiotensin system or whether tissue uptake of renin and localized production of Ang II might account for any cardiovascular, renal, hormonal or drinking effect of circulating renin. DESIGN: Intravenous infusions of renin (0.6 ng/min; n = 10) and Ang II (3.5 ng/min; n = 10) that produce similar plasma Ang II levels were compared for 2 weeks with vehicle (n = 7) in conscious rats after a 1-week control period. Mean arterial pressure (MAP) and the heart rate were measured continuously. Hormones and renal function were measured twice weekly. Plasma Ang II and recovery data were measured in seven additional rats. RESULTS: In renin- and Ang II-infused rats, respectively, plasma Ang II increased similarly from 4.5 +/- 0.8 and 4.4 +/- 0.9 to 10.8 +/- 0.7 and 10.6 +/- 0.7 pg/ml and declined similarly in the second week to 7.0 +/- 1.1 and 7.0 +/- 1.5 pg/ml. Plasma renin increased from 4.2 +/- 0.7 to 21.7 +/- 1.3 and fell from 5.9 +/- 0.5 to 0.6 +/- 0.2 ng/ml per h respectively. Plasma prorenin fell similarly (> 70%); angiotensinogen was unchanged. MAP rose initially by 25.6 +/- 1.2 and 23.3 +/- 0.9 mmHg and by an additional 21.1 +/- 2.4 and 27.4 +/- 1.8 mmHg on days 5-8. The heart rate fell gradually but transiently by -11% in both. Although the initial MAP rise was slower in renin-infused rats (P< 0.05) MAP returned to baseline within 2 h after both infusions were stopped. Changes in renal vascular resistance, renal blood flow, glomerular filtration rate, urinary sodium, potassium and water excretion and water intake were not significantly different between renin- and Ang II-infused rats. CONCLUSIONS: Intravenous infusions of low doses of renin or Ang II into conscious rats increase MAP identically. MAP increases in two phases 5-8 days apart, in coordination with transient falls in the heart rate. Renin- and Ang II-induced chronic hypertension are identically sustained by very small increases in plasma Ang II. Blood pressure increases more slowly with renin infusions, consistent with tissue binding. Notwithstanding, no evidence was obtained for a physiological role of tissue-bound renin in causing the cardiovascular, renal, hormonal and drinking responses measured in this study.
Angiotensin II↗
Appropriate regulation of human renin gene expression and secretion in 45-kb human renin transgenic mice.
To create physiological models of the human renin-angiotensin system in transgenic animals, the component genes should be expressed in the correct tissues and cells and respond appropriately to physiological stimuli. We recently showed that mice carrying a 45-kb human renin genomic fragment, containing approximately 25 kb 5'-flanking DNA and 6 kb 3'-flanking DNA, express the transgene in a highly cell- and tissue-specific pattern. More importantly, in contrast to previous models, human renin in the circulating plasma of these mice is derived exclusively from the kidneys. In the present study, we tested the responses of both human and mouse renal renin expression and secretion of the 45-kb hREN transgenic mice to a variety of physiological and pharmacological stimuli. A sodium-deficient diet, angiotensin-converting enzyme inhibition, and beta1-adrenergic stimulation each increased both human and mouse plasma renin concentration significantly, whereas elevated blood pressure and/or increased plasma angiotensin II levels suppressed them. Human and mouse renal renin mRNA levels changed similarly but to a lesser degree. These studies demonstrate that human renin synthesis and secretion respond appropriately in 45-kb hREN mice to physiological stimuli. This most likely results from appropriate cell-specific expression of the transgene conferred by the extended transgene flanking sequences.
Animals↗
Usefulness of subnormal midwall fractional shortening in predicting left ventricular exercise dysfunction in asymptomatic patients with systemic hypertension.
We have recently shown that a subgroup of asymptomatic hypertensive patients exhibit subnormal left ventricular (LV) midwall fiber shortening at rest and that this finding predicts morbidity and mortality independently of age, blood pressure (BP), or the presence of LV hypertrophy. However, it is unknown whether abnormal midwall fractional shortening predicts either subnormal LV functional reserve or extracardiac damage in asymptomatic hypertensive patients. Accordingly, we compared radionuclide cineangiographic LV ejection fraction at rest and maximum exercise as well as clinical findings between 89 patients with normal and 16 patients with subnormal midwall fractional shortening by echocardiogram. Patients with low midwall fractional shortening were similar in gender, age, and systolic BP to those with normal shortening but had higher mean diastolic BP and body mass indexes (both p < 0.05). The 2 groups also had similar resting ejection fraction (56 +/- 9% vs 55 +/- 15%, with normal or subnormal shortening, respectively, p = NS). Patients with subnormal midwall fractional shortening had higher LV mass and tended to have higher urinary protein excretion and serum creatinine levels. Subnormal LV ejection fraction with exercise (< 54%) was observed in 13 of 89 patients (15%) with normal midwall fractional shortening but in 7 of 16 patients (44%) with subnormal shortening (p < 0.05). Multiple linear regression analysis revealed that midwall fractional shortening independently predicted exercise performance (p < 0.001). Thus, subnormal midwall fractional shortening predicts depressed LV fractional reserve in asymptomatic hypertensive patients and may contribute to identification of patients with extracardiac target-organ damage.
Adult↗
Plasma renin activity: a risk factor for myocardial infarction in hypertensive patients.
To determine whether pretreatment plasma renin activity (PRA), without accompanying 24-h urine sodium, can predict myocardial infarction (MI), the PRA levels of 2,902 hypertensive patients [white (38%), male (65%), median age 55 years], with mean entry blood pressure (BP) of 150/97 mm Hg were examined. During an average 3.6 years follow-up (87% > or = 9 months), there were 55 MIs, 21 strokes, and 16 other cardiovascular disease (CVD) deaths. Classification of PRA levels into 3 renin strata [high (H) PRA > or = 4.5 (n = 354), normal (N) 0.75 to 4.49 (n = 1,622), and low (L) < 0.75 (n = 926) ng/mL/h] yielded subgroups that did not differ in LVH (9% v 11%) or smoking prevalence (26% v 25%) but high versus low PRA subjects included more aged < 55 years (64% v 53%); white (49% v 25%); men (79% v 52%); cholesterol > or = 6.3 mmol/L (33% v 25%); all P values < .01. MI rates per 1,000/year were H: 9.3, N: 5.5, L: 2.5 (H v L, RR = 3.8, 95% CI: 1.7 to 8.4). A similar relationship was seen with total CVD (H: 12.5, N: 9.3, L: 5.2; RR = 2.4, 95% CI: 1.3 to 4.5) and all-cause mortality (H: 7.0, N: 6.2, L: 2.5; RR = 2.8, 95% CI: 1.2 to 6.8) but not CVA (H: 1.6, N: 2.0, L: 1.9). In a Cox survival analysis only renin, age, sex, smoking, LVH, and cholesterol were significantly (P < .02) related to MI occurrence. There was, for every 2 unit increase in PRA, an overall 25% increase in MI incidence. Among hypertensive subjects, PRA level (without urine sodium), is independently and directly associated with the incidence of MI.
Black People↗
Serum sex hormone levels in postmenopausal women with hypertension.
In order to test the hypothesis that an alteration in the sex hormone milieu may underlie risk factors for myocardial infarction, fasting serum sex hormones, ie, estradiol, testosterone, free testosterone, and androstenedione, were measured in 24 hypertensive and in 19 healthy postmenopausal women. The mean serum free testosterone level (P=0.01) and the free-to-total testosterone ratio (P < 0.04) were increased in the women with hypertension. In a stepwise multiple regression analysis on the hypertensive and normotensive groups combined, with systolic blood pressure (SBP) as the dependent variable and body mass index, age, free testosterone, estradiol, insulin, and cholesterol levels as the independent variables, only free testosterone showed an independent relationship to SBP (P=0.009). The finding in the present study of an independent positive relationship of free testosterone with hypertension is consistent with a similar relationship of free testosterone with other risk factors for myocardial infarction in women found in previous studies and supports the hypothesis.
Aged↗
Midwall left ventricular mechanics. An independent predictor of cardiovascular risk in arterial hypertension.
BACKGROUND: An appreciable proportion of asymptomatic hypertensive patients have depressed left ventricular (LV) performance that is identified by midwall shortening/endsystolic stress relations but not by indexes that use endocardial shortening. It has not been established, however, whether depressed midwall ventricular performance has prognostic implications. METHODS AND RESULTS: Echocardiographic endocardial and midwall LV fractional shortening/circumferential end-systolic stress relations in 294 hypertensive patients were analyzed as predictors of the occurrence of cardiovascular morbid events that occurred in 50 patients (including 14 deaths) during a 10-year mean follow-up. Patients with initially lower midwall but not endocardial shortening, either in absolute terms or as a percentage of predicted from observed end-systolic stress, were more likely to suffer morbid events than those with initially normal values (P < .004). Cardiovascular events occurred in 29 of 100 patients (29%) and death in 10 of 100 patients (10%) among those who were in both the two highest quartiles of LV mass index and the two lowest quartiles of midwall shortening, as opposed to 21 of 194 (11%) and 4 of 194 (2.1%) of the remaining patients (odds ratio, 3.4; 95% CI, 1.8 to 6.3; P < .0001; and odds ratio, 5.3; 95% CI, 1.6 to 17.3; P < .006, respectively). In logistic analysis, increasing age, high LV mass, high systolic blood pressure, and low values for an interaction term between LV mass index and midwall shortening independently predicted cardiovascular events (.04 < P < .001); increasing age, low midwall LV shortening as a percentage of predicted, and high value of the interaction term predicted the occurrence of cardiac death (.004 < P < .0002). Survival analysis controlling for age confirmed that low midwall shortening independently predicted cardiac morbidity or death, especially in the subgroup of patients with LV hypertrophy. CONCLUSIONS: Depressed midwall shortening is a predictor of adverse outcome in arterial hypertension; the combination of higher LV mass and lower midwall shortening identifies individuals at markedly increased risk.
Adult↗
Reduction of development of left ventricular hypertrophy in salt-loaded Dahl salt-sensitive rats by angiotensin II receptor inhibition.
To determine the effect of the angiotensin II AT1 receptor antagonist losartan (DuP753) on echocardiographic left ventricular (LV) anatomy in Dahl rats on high sodium diet, 27 Dahl salt-sensitive (Dahl-S, 13 on drug and 14 receiving tap water) and 27 Dahl salt-resistant rats (Dahl-R, 13 on drug and 14 receiving tap water) were studied by M-mode echocardiography during 8 weeks of 8% NaCl diet. At the endpoint (after 8 weeks or the last echocardiogram for animals who died earlier), Dahl-S receiving losartan had lower LV mass (1.6 +/- 0.4 g/kg 0.59) than Dahl-S receiving tap water (2.2 +/- 0.7 g/kg 0.59; P < .005), although blood pressure was only partially reduced (167 +/- 29 v 195 +/- 52; P = .05). This difference was mainly due to lower LV wall thickness (P < .02), with a less consistent decrease in LV chamber size in Dahl-S receiving losartan. Blood pressure was normal in Dahl-R (tap water group = 116 +/- 11 mm Hg; losartan group = 115 +/- 13 mm Hg) and losartan had no effect on LV mass (1.6 +/- 0.4 g/kg 0.59) in both groups). In the majority of rats, echocardiographic measurements were compared between the end of second or third week and the last available study: LV mass increased in salt-loaded Dahl-S receiving tap water (1.6+/- 0.6 to 2.1 +/- 0.7 g/kg 0.59, P < .04) and was stable in Dahl-S receiving losartan (1.5 +/- 0.1 to 1.5 +/- 0.3 g/kg 0.59), paralleling changes in LV chamber dimension. Thus, a high salt diet leads to hypertension and eccentric LV hypertrophy in Dahl-S but not in Dahl-R. Inhibition of angiotensin II AT1 receptors reduces the development of LV hypertrophy in Dahl-S rats despite lack of efficient control of blood pressure.
Analysis of Variance↗
Calcium antagonists and cardiovascular prognosis: a homogeneous group?
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Calcium Channel Blockers↗
Plasma renin activity and plasma prorenin are not suppressed in hypertensives surviving to old age.
An age related decline in plasma renin activity (PRA) has been described in normotensive and hypertensive subjects. Moreover, hypertensive patients are reported to have lower plasma prorenin levels. We therefore investigated whether that pattern of renin and prorenin suppression was apparent in white hypertensives and normotensives surviving to an older age. The study population consisted of 65 untreated hypertensives (office blood pressure > or = 160/95 mm Hg; mean age 79 +/- 6 SD; range 69 to 94 years) and 26 normotensives (mean age 77 +/- 8; range 66 to 99 years). The PRA in this population of older hypertensives (1.7 +/- 1.6 ng/mL/h) was not significantly different from normotensives of similar age (1.5 +/- 0.8 ng/mL/h). PRA was not correlated to age in either normotensives and hypertensives, but was inversely correlated to office blood pressure in the hypertensives (r = -0.25; P = .05). Plasma prorenin was also not significantly lower in older hypertensives (14.6 +/- 8.6 ng/mL/h) than in the normotensive controls (15.1 +/- 7.0 ng/mL/h). In normal subjects, but not in hypertensive patients, there was a positive relationship between plasma prorenin and age (r = 0.82; P < .001). However, elderly normotensive men had lower plasma prorenin levels (11.6 +/- 4.1 ng/mL/h) than normotensive women (18.6 +/- 7.4 ng/mL/h; P < .05). "Total renin" (PRA + plasma prorenin) was also lower in elderly normotensive men compared to women (13.2 +/- 3.9 ng/mL/h v 20.0 +/- 7.5 ng/mL/h; P < .05). In conclusion, neither PRA nor plasma prorenin are suppressed in normotensive or hypertensive subjects who survive to an old age. However, since an inverse relationship between PRA and age has been reported, it remains to be determined whether the renin/prorenin parameters were suppressed at any time or if normal renin and normal prorenin patients preferentially survive to an old age. The wide spectrum of plasma renin levels in the elderly indicates that treatment of these patients too can profitably be guided by pretreatment plasma renin levels.
Aged↗
Specific prorenin/renin binding (ProBP). Identification and characterization of a novel membrane site.
Renin can be detected in cardiovascular and other tissues but it disappears after bilateral nephrectomy indicating that tissues can take up or bind renal renin from the circulation. If renin uptake is the result of specific binding, plasma prorenin may be a natural antagonist of tissue directed renin-angiotensin systems. To investigate if specific prorenin/renin uptake occurs in rat tissues, binding studies were performed, with rat microsomal membrane preparations using recombinant rat prorenin metabolically labeled with 35S-methionine as a probe. A high affinity binding site for both renin and prorenin was identified. Affinities for prorenin and renin were approximately 200 and 900 pmol/L, respectively. Binding was reversible, saturable, and pH and temperature dependent. The relative binding capacities of membranes from various rat tissues were as follows (fmol/mg): renal cortex (55), liver (54), testis (63), lung (31), brain (18), renal medulla (15), adrenal (17), aorta (7), heart (4), and skeletal muscle (1). Bound prorenin was displaced by rat and human renin or prorenin but not by the prosequence of rat prorenin, angiotensin I or II, rat or human angiotensinogen, the renin inhibitor SQ30697, atrial natriuretic factor, amylase, insulin, bovine serum albumin, hemoglobin, heparin, lysozyme, ovalbumin, cytochrome C, pepsin, pepsinogen, ribonuclease A, mannose-6-phosphate, alpha-methyl mannoside, gonadotropin releasing hormone, or an antibody to hog renin binding protein. these results demonstrate specific binding of prorenin to a site in rat tissues, herein named ProBP, that also binds renin. It is possible that differences in prorenin/renin binding capacity determine the activity of tissue-directed renin-angiotensin systems and that prorenin is a natural antagonist. Alternatively, a prorenin/renin receptor may have been identified that may function by transducing an intracellular signal.
Amino Acid Sequence↗
Midwall LV mechanics in rats with or without renovascular hypertension: effect of different Na+ intakes.
Supranormal left ventricular (LV) function has been reported in one-kidney, one-clip (1K,1C) and two-kidney, one-clip (2K,1C) Goldblatt hypertension. However, this finding might be at least partially due to mismatching endocardial rather than midwall fractional shortening to mean end-systolic stress. Accordingly, relations of echocardiographic endocardial and midwall shortening to circumferential end-systolic stress were calculated in 40 Wistar rats on 0.4% NaCl (r = -0.92, SE of estimate = 4.3% and r = -0.62, SE of estimate = 3.2%, both P < 0.0001). Midwall shortening as a percentage of predicted was related to LV chamber diameter in normal animals (r = 0.56, P < 0.0001). Endocardial and midwall shortening were compared as percentage of the normal values predicted from wall stress in 34 2K,1C and 19 1K,1C on 0.4% Na+ 8-9 wk after surgery. Use of midwall shortening reduced the number of these hypertensive rats with supranormal observed-to-predicted shortening ratio from 28 to 7.5% (P < 0.0001). Salt-deprived and high-salt diets (0.0035 and 4% NaCl, respectively) were given to 16 and 18 additional controls, 9 and 7 2K,1C, and 7 and 7 1K,1C. Salt-deprived sham animals had greater endocardial and midwall shortening (106 +/- 7 and 111 +/- 10% of predicted, both P < 0.002) than sham rats on 0.4% NaCl, whereas 4% NaCl had no effect. Five of sixteen salt-deprived sham rats had supranormal observed-to-predicted midwall shortening ratios for LV chamber size, suggesting an enhanced inotropic state. Salt-deprived and high-salt diets had negligible effects on LV performance in Goldblatt rats. Thus use of midwall shortening reduces the number of renovascular hypertensive rats with apparently increased LV function. Salt deprivation stimulates LV myocardial function in normal rats independent of chamber dimension (i.e., an indirect measure of preload) but does not influence LV performance in Goldblatt hypertension 8 wk after renal artery clipping.
Animals↗
Plasma and renal prorenin/renin, renin mRNA, and blood pressure in Dahl salt-sensitive and salt-resistant rats.
We measured plasma prorenin and renin levels, renal renin mRNA, renal anti-renin and anti-prorenin-prosequence immunoreactivity, and blood pressure in maturing Brookhaven Dahl salt-sensitive (Dahl S) and salt-resistant (Dahl R) rats during 14 days of low (0%), medium (0.4%), or high 4%) NaCl diets. Blood pressure was higher in Dahl S rats and did not increase with high NaCl. Seven-week-old Dahl R rats had twofold and sixfold higher levels of plasma prorenin and renal prosequence immunoreactivity, respectively, which by 9 weeks were the same as in Dahl S rats. The anti-renin antiserum, BR1-5, was found to detect prorenin better than renin; Dahl S rats had suppressed renal anti-renin immunoreactivity relative to Dahl-R rats. Dahl R rats were unresponsive to high NaCl, whereas in Dahl S rats, plasma renin and renal prosequence immunoreactivity fell by 90% (P < .01), renal anti-renin immunoreactivity and renal renin MRNA fell by 35% (P < .05 for both), and plasma prorenin fell by 30% (P = NS). NaCl depletion increased prorenin/renin parameters similarly in both strains. There were direct relationships among all of the prorenin/renin parameters. Between low and high salt diets in Dahl S rats, plasma renin increased 20-fold, plasma total renin (renin plus prorenin) and renal renin mRNA both increased threefold, and plasma prorenin increased twofold. The results indicate that under steady-state conditions, plasma and renal renin/prorenin parameters change concordantly and that plasma total renin (renin plus prorenin) reflects changes in renal renin mRNA. The lower blood pressure of Dahl R rats is associated with later maturation-related declines in plasma and renal prorenin. Suppression of plasma renin may delay the salt-induced blood pressure rise in Dahl S rats. Finally, the renin system and blood pressure of Dahl R rats have remarkable disregard for a high salt diet.
Animals↗