bluuebunny/crossref_metadata_2025 huggingface dataset:
Saralasin-induced renin release: its blockade by prostaglandin synthesis inhibitors in the conscious rat.
Authors: Campbell W B , Jackson E K , Graham R M
Published: June 2012

The angiotensin antagonist, saralasin, (10 and 30 mg/kg), increased serum renin activity (SRA) in normal, conscious rats from 2.7 +/- 0.4 to 16.2 +/- 3.7 and 22.5 +/- 2.4 ng/ml/hr (p less than 0.001), respectively, without markedly altering blood pressure or heart rate. Indomethacin, in a dose which inhibited the urinary excretion of prostaglandin E2 (PGE2) by 75%, and arachidonate-induced hypotension by 83%, failed to alter basal SRA but inhibited saralasin-induced renin release by 99% and 87% at the 10 and 30 mg/kg doses, respectively. Indomethacin failed to alter basal hemodynamics or the hemodynamic response to saralasin. Propranolol (1.5 mg/kg) inhibited saralasin-induced renin release by 93% and enhanced the suppressant effect of indomethacin from 79% to 100%. Meclofenamate, another prostaglandin synthesis inhibitor, also blocked saralasin-induced renin release by 99% and 72% at the 10 and 30 mg/kg doses, respectively (p less than 0.001). In sodium-depleted rats, saralasin (0.3 mg/kg) increased SRA from 12 +/- 2 to 119 +/- 6 ng/ml/hr (p less than 0.001) and decreased blood pressure by 6% (p less than 0.01). In these animals, indomethacin failed to alter basal SRA, but inhibited saralasin-induced renin release by 82%, urinary excretion of PGE2 by 79%, and arachidonate-induced hypotension by 81%. These findings suggest 1) that saralasin-induced renin release is mediated by renal prostaglandins, and 2) an interrelationship exists between the receptor controlling AII-mediated inhibition of renin release, which is blocked by saralasin, and the juxtaglomerular beta-adrenergic receptor.
Effects of hydrochlorothiazide and diltiazem on reflex vasoconstriction in hypertension.
Authors: Mohanty P K , Sowers J R , Thames M D
Published: June 2012

The purpose of our study was to determine the effects of treatment with hydrochlorothiazide (n = 10) or diltiazem (n = 8) on reflex humoral, hemodynamic, and vascular responses to graded lower body negative pressure in subjects with mild to moderate hypertension (supine diastolic pressure, 95-114 mm Hg). All subjects received placebo for 2 to 4 weeks followed by either hydrochlorothiazide (25-50 mg b.i.d.) or diltiazem (120-180 mg b.i.d.) to achieve a reduction in supine diastolic pressure of 10 mm Hg or more and a final pressure below 90 mm Hg. Mean arterial pressure, forearm vascular resistance, plasma norepinephrine, and renin responses to graded lower body negative pressure (-10, -20, -40 mm Hg) and head-up tilt were examined before and after 12 weeks of treatment with either drug. Pretreatment basal values of mean arterial pressure (114 +/- 2 vs 117 +/- 2 mm Hg), forearm vascular resistance (29 +/- 3 vs 35 +/- 7 units), and plasma renin activity (0.7 +/- 0.2 vs 0.6 +/- 0.2 ng angiotensin I/ml/hr) were not significantly different between groups. There were no significant differences in basal plasma norepinephrine or in the increases of norepinephrine in response to lower body negative pressure before and after treatment in either group. Forearm vascular resistance responses to lower body negative pressure were virtually abolished in the diltiazem-treated group but not in the hydrochlorothiazide-treated group despite similar levels of mean arterial pressure and basal forearm vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)
Cardiovascular and renal profile of acute peripheral dopamine1-receptor agonism with fenoldopam.
Authors: Glück Z , Jossen L , Weidmann P , Gnädinger M P , Peheim E
Published: June 2012

Whether the dopaminergic system may be involved in essential hypertension is of pathogenetic as well as therapeutic interest. Therefore, we investigated in eight hypertensive and 12 normal subjects cardiovascular, endocrine, and renal responses to fenoldopam, which has been characterized experimentally as an agonist of peripheral postsynaptic dopamine1 receptors. A single oral dose of fenoldopam, 100 mg, changed blood pressure (BP) in hypertensive subjects (from 163/103 to 147/76 mm Hg; p less than 0.01 for systolic and p less than 0.001 for diastolic BP) and normal subjects (from 121/81 to 123/65 mm Hg; p less than 0.001 for diastolic BP); percentage decreases in diastolic BP averaged -20 +/- 6 and -16 +/- 7%, respectively. Fenoldopam-induced effects on other variables were similar in the two groups. Heart rate rose (p less than 0.001) on average from 69 to 92 beats/min in hypertensive and from 64 to 84 beats/min in normal subjects. Effective renal plasma flow increased (from 552 to 765 and 634 to 937 ml/min/1.73 m2; p less than 0.01), while glomerular filtration rate tended to decrease (from 121 to 99 ml/min/1.73 m2 in the hypertensive and from 119 to 97 ml/min/1.73 m2; p less than 0.001 in the normal group). Fractional sodium clearance was elevated (from 2.8 to 5.2 and 1.7 to 3.8%; p less than 0.01), as was free water clearance (from -1.7 to 0.6 and -1.7 to 0.1 ml/min/1.73 m2; p less than 0.01). Potassium clearance was largely unchanged. Plasma renin activity increased about twofold (p less than 0.01 in normal subjects), and plasma aldosterone by 40% (NS). Plasma norepinephrine levels increased twofold to 2.5-fold (p less than 0.001), and urinary norepinephrine excretion fivefold to 10-fold (p less than 0.01). Fenoldopam-induced changes were not significantly modified by intravenous and/or oral pretreatment with the dopamine-receptor antagonist metoclopramide or the cyclooxygenase inhibitor indomethacin. These findings suggest that in humans, fenoldopam may acutely override the dopaminergic antagonism of metoclopramide given in clinical dosage and that its cardiovascular and renal effects are not prostaglandin-mediated. Although acute sympathetic stimulation may be partially antagonistic, the concomitant BP-lowering, renal vasodilating, and natriuretic actions of fenoldopam represent a desirable profile of a potential antihypertensive agent.
Effects of chronic exercise on the coronary circulation in conscious rats with renovascular hypertension.
Authors: Wicker P , Abdul-Samad M , Rakusan K , Tarazi R C , Healy B
Published: June 2012

Since various studies suggest that chronic physical conditioning promotes myocardial vascularity, we investigated whether it could prevent the coronary reserve abnormalities of hypertensive cardiac hypertrophy. One week after operation, female Sprague-Dawley rats with two-kidney, one clip Goldblatt hypertension were either subjected to a moderate exercise program by swimming (n = 21) or kept sedentary (n = 16) for 9 weeks. Sedentary (n = 16) and exercised (n = 15) sham-operated rats served as controls. Maximal coronary blood flow and minimal coronary resistance, either per unit mass or for the entire left ventricle, an index of the functional cross-sectional area of the coronary resistance vessels, were determined in conscious, unrestrained rats by left atrial microsphere injection following maximal vasodilation with carbochrome (12 mg/kg). Following exercise, left ventricular mass was moderately (+5-10%) but significantly increased in normotensive rats, whereas left ventricular hypertrophy was significantly accentuated in the hypertensive rats. Minimal coronary resistance for the entire left ventricle was significantly decreased (-24%) in normotensive rats but did not change significantly in hypertensive rats. Minimal coronary resistance per unit mass (the coronary vasodilator reserve) tended to decrease in normotensive rats (-17%), whereas it tended to be further augmented in hypertensive rats (+13%). However, these differences were marginally significant and were not associated with any changes in maximal coronary blood flow per unit mass (the coronary flow reserve). Thus, in normal rats, exercise promoted myocardial arterial vascularity in parallel with the development of cardiac hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)
Fatty acid binding protein in kidney of normotensive and genetically hypertensive rats.
Authors: Fujii S , Kawaguchi H , Yasuda H
Published: June 2012

Fatty acid binding protein was purified from renal medulla, and its binding activity and fatty acid composition were determined in spontaneously hypertensive stroke-prone rats (SHRSP). Wistar-Kyoto rats (WKY) were used as controls. Fatty acid binding activity was higher in 5-week-old prehypertensive SHRSP than in control WKY (0.155 +/- 0.006 vs 0.030 +/- 0.001 mol palmitic acid/mol protein). However, in 40-week-old rats, the activity was decreased only in SHRSP with established hypertension (0.035 +/- 0.002 vs 0.028 +/- 0.003 mol palmitic acid/mol protein WKY). Fatty acid compositions were similar among 5-week-old and 40-week-old control WKY and 5-week-old SHRSP (palmitic acid, 24%; stearic acid, 14%; oleic acid, 30%; linoleic acid, 29%; arachidonic acid, 3%), although the total amount of bound long-chain fatty acids was decreased in 5-week-old SHRSP, explaining the high fatty acid binding activity in this preparation. Fatty acid binding protein from 40-week-old SHRSP had an elevated proportion of endogenous arachidonic acid, with other fatty acids being relatively reduced (palmitic acid, 8%; stearic acid, 2%; oleic acid, 4%; linoleic acid, 10%; arachidonic acid, 76%), indicating increased arachidonic acid transport in the cytosol. These results show that genetically hypertensive rats had an alteration in fatty acid transport mediated by fatty acid binding protein; this alteration may be involved in the pathogenesis of hypertension.
Arterial and venous compliance in sustained essential hypertension.
Authors: Safar M E , London G M
Published: June 2012

Arterial and venous compliances are decreased in men with sustained essential hypertension. The reduced arterial compliance acts to maintain systolic pressure and end-systolic stress, thus contributing to the development of cardiac hypertrophy. Since cardiac output remains within the normal range in the hypertrophied hypertensive heart, elevated left ventricular pressures, and therefore increased cardiac filling pressures, are necessary if an adequate stroke volume is to be maintained. In hypertensive persons, reduced venous compliance acts to maintain the filling pressure of the heart in the presence of reduced intravascular volume. In patients with hypertension, even if compliance changes have been initiated by the elevated blood pressure itself, the reduced arterial and venous compliance observed in cross-sectional studies is not simply the mechanical consequence of the elevated blood pressure, but also reflects intrinsic alterations of the vascular wall. Consequently, blood pressure reduction caused by antihypertensive agents is not constantly associated with a reversion of the decreased vascular compliance. Such observations may be of importance in the consideration of cardiovascular morbidity and mortality in patients treated for hypertension.
Development and application of a simple microassay for adenosine in rat plasma.
Authors: Jackson E K , Ohnishi A
Published: June 2012

Adenosine may be a physiological modulator of vascular smooth muscle tone, sympathetic neurotransmission, renin release, and renal and cardiac function. To facilitate the elucidation of the physiological role of adenosine, a microassay for adenosine was developed that allows accurate quantitation of adenosine in 75 microliters of rat plasma, thus permitting multiple determinations of plasma adenosine levels in an individual rat without inducing hemodynamic perturbations due to blood loss. The technique employs a simple and rapid extraction of plasma with a reverse-phase Sep-Pak cartridge and exploits the increased mass sensitivity of microbore high performance liquid chromatography. The assay was verified by demonstrating a linear relationship between the amount of adenosine added to plasma and the amount detected by the assay, a linear relationship between the rate of adenosine infusion into rats and plasma adenosine levels, and the absence of measurable adenosine levels in plasma incubated with adenosine deaminase. The mean arterial plasma level of adenosine in the anesthetized rat was determined to be 119 +/- 28 (SD) ng/ml (n = 10). With the use of this assay, renal venous plasma levels of adenosine were found to be elevated sixfold in two-kidney, one clip Goldblatt hypertensive rats (1 week postclipping) compared with sham-operated controls. Given the known effects of adenosine on renin release, these data support a role for endogenous adenosine as a regulator of renin release in renovascular hypertension.
Plasma nonesterified fatty acids in the Dahl rat. Response to salt loading.
Authors: Kelly R A , Pfeffer J M , Mitch W E , Smith T W
Published: June 2012

The link between dietary salt intake and the development of hypertension in the salt-sensitive Dahl strain of rats remains elusive. There is evidence that Dahl salt-sensitive rats (DS) produce less vasodilator and natriuretic prostaglandins in response to salt loading than do control salt-resistant rats (DR), although the reason for this blunted response is unknown. We examined the effects of chronic dietary salt loading on the plasma levels of nonesterified fatty acids in DS and DR. Animals were fed the same chow containing either 0.4% or 4% NaCl (wt/wt). At 12 weeks, 75 microliters of tail capillary blood was obtained from restrained, conscious rats, and principal nonesterified fatty acids were measured by high performance liquid chromatography. Total nonesterified fatty acids rose in the 15 DR on high salt diets compared with values in 11 rats eating low salt (0.57 +/- 0.05 vs 0.35 +/- 0.01 mM; p less than 0.001). The greatest changes occurred in levels of arachidonic acid (+287%) and in the arachidonic precursors, linoleic (+89%) and linolenic (+107%) acids. In marked contrast, there was no change in levels of plasma nonesterified fatty acids in DS fed 4% NaCl compared with DS fed 0.4% NaCl. These observations suggest that defective production of natriuretic and vasodilator prostaglandins by DS may be due in part to an inability to produce or release eicosanoid precursors from phospholipid stores in response to dietary salt.
Structural and functional consequence of neonatal sympathectomy on the blood vessels of spontaneously hypertensive rats.
Authors: Lee R M , Triggle C R , Cheung D W , Coughlin M D
Published: June 2012

Neonatal sympathectomy of spontaneously hypertensive rats (SHR) and control Wistar-Kyoto rats (WKY) was performed by a combined treatment with antiserum to nerve growth factor and guanethidine during the first 4 weeks after birth. The development of hypertension was completely prevented in the treated SHR: at 28 to 30 weeks of age, systolic blood pressure of treated SHR was 139 +/- 2 mm Hg as compared with 195 +/- 8 mm Hg in untreated SHR. The extent of sympathectomy was verified by histofluorescence. Fluorescence histochemistry for catecholamine-containing nerves showed a complete absence of adrenergic nerves in the mesenteric arteries of treated rats. A supersensitivity to norepinephrine was exhibited by mesenteric arteries, anococcygeus muscle, and tail arteries from the treated SHR and WKY. In the mesenteric vascular bed, maximal response to norepinephrine was significantly reduced by sympathectomy. Sympathectomy also abolished the responses (e.g., generation of excitatory junctional potentials) of tail arteries to electrical stimulation of perivascular nerves. Morphometric measurements of three categories of mesenteric arteries showed that sympathectomy had no effect on the hypertrophic change of smooth muscle cells in the conducting vessels, but it prevented the hyperplastic changes of the muscle cells from reactive, muscular arteries and small resistance vessels. These results suggest that one of the primary roles of the overactive sympathetic nervous system in the development of hypertension in SHR is manifested through its trophic effect on the arteries of SHR. This trophic effect appears to cause a hyperplastic change in the smooth muscle cells in the reactive and resistance vessels, thereby contributing to the development of hypertension in older SHR.
Renin suppression by saline is blunted in nonmodulating essential hypertension.
Authors: Rabinowe S L , Redgrave J E , Shoback D M , Podolsky S , Hollenberg N K , Williams G H
Published: June 2012

We have reported that 50% of subjects with normal renin essential hypertension have both delayed suppression of the renin-angiotensin-aldosterone axis following sodium infusion and a delayed rate of excretion of an acute salt load. In another study we have also described a subset of patients with essential hypertension (called nonmodulators) who have several abnormalities, including a pressor response to salt loading. To evaluate whether the abnormalities described in these different groups of patients actually occur in the same patient, we assessed the renin-angiotensin-aldosterone axis response to short-term saline loading in 38 hypertensive patients. Their ability to modulate was determined by their renal vascular response to infused angiotensin II on a high salt diet (200 mEq Na). In response to a 3-hour infusion of saline, 75 mEq/hr, the reduction in plasma renin activity at both 60 and 120 minutes was significantly greater (p less than 0.008) in patients with normal modulation than in the nonmodulators. Plasma aldosterone levels were also significantly lower (p less than 0.001) in those with intact modulation. Thus, nonmodulating essential hypertensive patients have abnormalities in several systems that influence sodium homeostasis, including altered adrenal and renal vascular response to angiotensin II, altered renal blood flow response to salt loading, and a delayed suppression of the renin-angiotensin-aldosterone system with short-term saline infusion.
Pregnancy hypertension, blood pressure during labor, and blood lead levels.
Authors: Rabinowitz M , Bellinger D , Leviton A , Needleman H , Schoenbaum S
Published: June 2012

Pregnancy hypertension, blood pressure during labor, and the umbilical cord blood lead concentration were assessed in 3851 women for whom additional demographic, medical, and personal information was available. Lead levels correlated with both systolic (Pearson r = 0.081, p = 0.0001) and diastolic (r = 0.051, p = 0.002) blood pressures during labor. The incidence of pregnancy hypertension increased with lead level. Multivariate models of pregnancy hypertension and systolic blood pressure as a function of maternal age, parity, hematocrit, ponderal index, race, and diabetes were improved by including lead as a predictor variable. At these observed levels of exposure (mean blood lead, 6.9 +/- 3.3 [SD] micrograms/dl), lead appears to have a small but demonstrable association with pregnancy hypertension and blood pressure at the time of delivery, but not with preeclampsia.
Osmotic regulation of vasopressin and renin in spontaneously hypertensive rats.
Authors: Sladek C D , Chen Y H , Aravich P F , Blair M L
Published: June 2012

Abnormalities in the vasopressin and renin systems have been reported in spontaneously hypertensive rats (SHR). Therefore, studies were performed to evaluate the responsiveness of these systems to changes in plasma osmolality and sodium concentration. These variables were manipulated in vivo by intraperitoneal administration of distilled water, isotonic saline, or hypertonic saline to 8- and 18-week-old SHR and normotensive Wistar-Kyoto rats (WKY). Animals were decapitated 30 minutes later, and trunk blood was collected. The hypertonic saline injections resulted in an increase in plasma osmolality and serum sodium at both ages (p less than 0.001). Serum vasopressin was higher in all groups of animals receiving hypertonic saline (1200 mosm/kg H2O; p less than 0.05), but the magnitude of increase was not significantly different in the SHR and WKY at either age. Serum renin activity was lower in SHR than in WKY following acute decreases in serum sodium at 8 weeks, but it was the same for both strains at 18 weeks. Both kidney renin content and concentration were lower in SHR than in WKY at 18 weeks but not at 8 weeks. Therefore, the suppressed renin response to acute osmotic challenge in 8-week-old SHR is not the consequence of reduced kidney renin content. The vasopressin response to osmotic stimulation also was evaluated in vitro using hypothalamoneurohypophyseal explants obtained from 5-, 8-, and 18-week-old SHR and WKY.(ABSTRACT TRUNCATED AT 250 WORDS)
Antihypertensive effects of an aromatase inhibitor in the spontaneously hypertensive rat.
Authors: Melby J C , Holbrook M , Griffing G T , Johnston J O
Published: June 2012

Recent studies from this laboratory have demonstrated that 19-nor-deoxycorticosterone, a potent mineralocorticoid, has been excreted in excess in the urine of young spontaneously hypertensive rats (SHR). Although urinary 19-nor-deoxycorticosterone levels decline before the onset of hypertension, preliminary evidence suggests that 19-nor-deoxycorticosterone is further oxygenated to other steroid products in older SHR. Since 19-hydroxylation is the essential first step in the formation of 19-nor-deoxycorticosterone from deoxycorticosterone and since the mechanism-based aromatase inhibitor 10-propargyl-androst-4-ene,3,17-dione preferentially inhibits 19-hydroxylation, this agent was administered to weanling SHR to determine whether inhibition of 19-nor-deoxycorticosterone formation could modify or prevent hypertension. Accordingly, either 10 mg of 10-propargyl-androst-4-ene,3,17-dione or vehicle (control) was injected daily for several weeks in 4.5 week-old SHR. Injection of 10-propargyl-androst-4-ene,3,17-dione reduced urinary free 19-nor-deoxycorticosterone and retarded the development of hypertension compared with the effect of vehicle injection (p less than 0.05). Mean blood pressure levels in SHR receiving 10-propargyl-androst-4-ene,3,17-dione were lower than those in SHR receiving vehicle for each of the first 8 weeks of treatment (p less than 0.05). These data support the importance of 10-nor-corticosteroids in the pathogenesis of hypertension in SHR.
Fructose-induced insulin resistance and hypertension in rats.
Authors: Hwang I S , Ho H , Hoffman B B , Reaven G M
Published: June 2012

To determine if hypertension could be produced in normal rats by feeding them a fructose-enriched diet, Sprague-Dawley rats were fed either normal chow or a diet containing 66% fructose as a percentage of total calories for approximately 2 weeks. At the end of this period systolic blood pressure had increased from 124 +/- 2 to 145 +/- 2 (SEM) mm Hg in the fructose-fed rats, whereas no change occurred in the control group. In addition, hyperinsulinemia and hypertriglyceridemia were associated with hypertension in fructose-fed rats. The addition of clonidine to the drinking water inhibited fructose-induced hypertension, but not the increase in plasma insulin or triglyceride concentration seen in fructose-fed rats. Thus, the metabolic changes associated with fructose-induced hypertension are unlikely to be secondary to an increase in sympathetic activity. Whether or not this is also true of the hypertension remains to be clarified.
Inverse relationship between heart rate and blood pressure variabilities in rats.
Authors: Ferrari A U , Daffonchio A , Albergati F , Mancia G
Published: June 2012

The interplay of heart rate variability, baroreceptor control of heart rate, and blood pressure (BP) variability was examined in chronically instrumented, unanesthetized, freely moving rats in which the efferent neural influences on heart rate were pharmacologically altered. In each rat, BP was recorded continuously for 90 minutes in the control condition and in one or more of the following conditions: 1) beta-adrenergic receptor blockade by propranolol, 1 mg/kg; 2) cholinergic blockade by atropine, 0.75 mg/kg, and 3) combined blockade by propranolol plus atropine. Each BP recording was analyzed beat-to-beat by a computer that calculated heart rate and BP variabilities, both expressed as variation coefficients. In addition, under each condition the sensitivity of the arterial baroreceptor control of heart rate was assessed by measuring the reflex changes in pulse interval in response to BP changes induced by bolus i.v. injections of phenylephrine and nitroprusside. As compared with the control condition, 1) propranolol (n = 10) reduced heart rate variability by 23 +/- 4% (p less than 0.01), only slightly impaired baroreceptor reflex sensitivity, and did not significantly modify BP variability (+11 +/- 7%); 2) atropine (n = 11) reduced heart rate variability by 30 +/- 7% (p less than 0.01), drastically impaired baroreceptor reflex sensitivity, and increased BP variability (+40 +/- 8%, p less than 0.01); 3) combined blockade (n = 10) caused variability and baroreceptor reflex changes similar to those induced by atropine alone. Thus, heart rate variability depends on both vagal and sympathetic influences. However, only the former component affects BP variability, that is, it plays an antioscillatory role.(ABSTRACT TRUNCATED AT 250 WORDS)
Enhanced forearm blood flow during mental stress in children of hypertensive parents.
Authors: Anderson E A , Mahoney L T , Lauer R M , Clarke W R
Published: June 2012

This study compared changes in forearm blood flow, forearm vascular resistance, blood pressure, and heart rate elicited by mental stress (mental arithmetic) in 12 adolescents with a hypertensive parent and 13 age-matched adolescents with normotensive parents. The two groups did not differ in resting forearm blood flow, forearm vascular resistance, heart rate, or blood pressure. During mental stress, children with a family history of hypertension had a significantly greater increase in forearm blood flow than did children of normotensive parents (+37.5 +/- 8.0 vs +12.8 +/- 7.5%; p less than 0.05) and a trend toward reduced forearm vascular resistance (p = 0.08). Mental stress significantly increased systolic blood pressure (p less than 0.0001), diastolic blood pressure (p less than 0.001), and heart rate (p less than 0.03) in both groups. The blood pressure and heart rate responses to stress were not significantly different between groups. There was no evidence of a prolonged response or a different pattern of recovery in children with a family history of hypertension. This study indicates that regional blood flow responses underlying similar blood pressure increases during mental stress may be different in adolescents with and without a family history of hypertension.
Correlates of plasma atrial natriuretic factor in health and hypertension.
Authors: Montorsi P , Tonolo G , Polonia J , Hepburn D , Richards A M
Published: June 2012

Plasma concentrations of atrial natriuretic factor (ANF) were compared in normotensive subjects and subjects with untreated, uncomplicated essential hypertension (n = 21 pairs) matched for age, sex, and race. Plasma peptide values were slightly greater (45 +/- 3 vs 36 +/- 3 pg/ml; p less than 0.05) in the hypertensive group. On univariate analysis, age (r = 0.52, n = 47, p less than 0.001) and creatinine clearance (r = -0.30, n = 47, p less than 0.05) were significantly related to plasma ANF concentrations, but arterial pressure was not (r = 0.14, n = 47), in an extended group of normal subjects. In contrast, plasma ANF values were related to arterial pressure in both an extended group of subjects with untreated essential hypertension (r = 0.54, n = 38, p less than 0.001) and in our total heterogeneous pool of hypertensive patients (r = 0.46, n = 79, p less than 0.001), but weak positive associations with age and inverse relationships with creatinine clearance were not statistically significant in either hypertensive group. Similar weak inverse relationships between plasma ANF values and renin-angiotensin-aldosterone system activity were found in both normal and hypertensive subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of captopril and hydralazine on arterial pressure-urinary output relationships in spontaneously hypertensive rats.
Authors: Kline R L , Mercer P F
Published: June 2012

Angiotensin I converting enzyme inhibitors are typically classified as peripheral vasodilators. We studied the effect of captopril and a known vasodilator, hydralazine, on arterial pressure-urinary output relationships in adult spontaneously hypertensive rats to determine whether these drugs produced similar changes in this relationship. Tail-cuff pressure and 24-hour urine output and sodium excretion were measured under steady state conditions during ingestion of tap water or saline (1% NaCl) ad libitum. Sodium intake increased seven to nine times when rats drank saline, but in the absence of drug treatment, tail-cuff pressure was not altered significantly (water, 213 +/- 3 vs saline, 220 +/- 5 mm Hg). Daily administration of captopril (100 mg/kg p.o.) or hydralazine (15 mg/kg p.o.) for 2 weeks lowered tail-cuff pressure significantly (175 +/- 3 and 166 +/- 3 mm Hg, respectively; p less than 0.01) while rats drank tap water. Continued administration of hydralazine plus 2 weeks of drinking saline did not alter tail-cuff pressure (162 +/- 4 mm Hg), but with the addition of saline during captopril treatment, tail-cuff pressure was elevated significantly (210 +/- 5 mm Hg; p less than 0.01). Thus, hydralazine produced a parallel shift of the arterial pressure-urinary output relationship along the pressure axis. In contrast, captopril produced a marked change in the slope of this relationship, making arterial pressure extremely salt-sensitive. The results suggest that the two drugs have different effects on the mechanisms that contribute to the long-term control of arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Altered erythrocyte and plasma sodium and potassium in hypertension, a facet of hyperinsulinemia.
Authors: Halkin H , Modan M , Shefi M , Almog S
Published: June 2012

Red blood cell sodium and potassium, plasma potassium, glucose and insulin responses to oral glucose load, serum urate, and plasma triglycerides were determined in a stratified subsample (n = 89) of a representative population sample (n = 1211), comprising 30 nonobese normotensive subjects with normal glucose tolerance (reference group) and 59 subjects representing each of the seven possible combinations of abnormal glucose tolerance, obesity, and hypertension. Rate of cation imbalance (red blood cell sodium greater than or equal to 7.0 mEq/L, potassium less than 92.5 mEq/L, or plasma potassium greater than or equal to 4.5 mEq/L) was 88.1% in subjects with abnormal tolerance, obesity, or hypertension, as compared with 40.0% in the reference group (p less than 0.001). These subjects were also characterized by significantly greater rates of insulin response: 60- and 120-minute postload levels of 100 mU/L or more (88.1 vs 46.7%), plasma triglycerides of 80 mg/dl or more (89.8 vs 53.3%) and serum uric acid of 5.5 mg/dl or more (61.0 vs 26.7%; p less than 0.001 for all). The rate of cation imbalance was significantly associated with each of these three biochemical correlates: insulin response (p less than 0.01), triglycerides (p less than 0.001), and urate (p less than 0.001). In the total population sample, the rate of untreated hypertension increased from 18% to 35% to 55.3% (p less than 0.001), with an increase in the number of biochemical correlates of cation imbalance in combination with glucose intolerance and obesity.(ABSTRACT TRUNCATED AT 250 WORDS)
Enalapril attenuates natriuresis of atrial natriuretic factor in humans.
Authors: Gaillard C A , Koomans H A , Mees E J
Published: June 2012

We studied the effect of converting enzyme inhibition with enalapril on the natriuresis observed after administration of atrial natriuretic factor (human ANF-[99-126], given as a 100-micrograms bolus i.v. injection) in eight healthy humans consuming a 100 mmol sodium diet. Without enalapril, sodium excretion rose from 127 +/- 19 (mean +/- SE) to 437 +/- 103 mumol/min in the first 20 minutes after ANF was administered. Clearance studies performed during maximal water diuresis indicated a rise in glomerular filtration rate (inulin clearance), free water clearance, phosphate, lithium, uric acid, and magnesium excretion. Four days of enalapril (20 mg b.i.d.) increased effective renal plasma flow (p-aminohippurate clearance) and reduced blood pressure (from 114/71 +/- 2/2 to 105/60 +/- 2/1 mm Hg). Under these conditions baseline sodium excretion was not different from the control study, but it rose less after ANF (from 117 +/- 22 to 242 +/- 63 mumol/min), and the increments in glomerular filtration rate, free water clearance, phosphate, lithium, uric acid, and magnesium were all blunted and nonsignificant. In addition, effective renal plasma flow tended to fall; this effect was not observed when ANF was given without enalapril. These results support the notion that the effects of ANF on renal hemodynamics and on tubular sodium handling depend on renal angiotensin II and that blood pressure reduction may interfere with the ANF-induced natriuresis.
The effect of captopril on renal blood flow in renal artery stenosis assessed by positron tomography with rubidium-82.
Authors: Tamaki N , Alpert N M , Rabito C A , Barlai-Kovach M , Correia J A , Strauss H W
Published: June 2012

The sequence and magnitude of acute changes in renal blood flow following administration of captopril were determined in a canine model of acute unilateral renal artery stenosis using rubidium-82 and positron emission tomography. Data were recorded in each of nine dogs under three conditions: 1) during a baseline control interval, 2) during renal artery stenosis, and 3) during stenosis with intravenous injection of captopril (1.2 mg/kg). Mean arterial blood pressure was 108 +/- 12 mm Hg at control, increased significantly to 125 +/- 13 mm Hg (p less than 0.01) during stenosis, and decreased to 98 +/- 13 mm/Hg (p less than 0.01) after captopril infusion. Mean renal blood flow was calculated using a steady state single compartment model from the images produced by positron emission tomography. The estimated flow to the affected kidney was 3.37 +/- 1.48 ml/min/g at control, 0.86 +/- 0.62 ml/min/g during stenosis (p less than 0.01), and 0.64 +/- 0.57 ml/min/g after captopril administration (p = NS compared with precaptopril value). The estimated flow to the contralateral kidney was minimally reduced from a baseline of 3.84 +/- 0.95 to 3.24 +/- 1.13 ml/min/g (p = NS) during stenosis and increased after captopril infusion (4.08 +/- 0.94 ml/min/g; p = 0.01). These data suggest that repetitive imaging with positron emission tomography can be used to delineate acute changes in renal perfusion following captopril administration.
Regional vascular effects of serotonin and ketanserin in young, healthy subjects.
Authors: Blauw G J , van Brummelen P , Chang P C , Vermeij P , van Zwieten P A
Published: June 2012

The local hemodynamic effects of serotonin (5-hydroxytryptamine; 5-HT) and the selective 5-HT2 antagonist ketanserin were investigated in the forearm of 20 healthy volunteers. Single doses of 5-HT (0.1-80 ng/kg/min) and ketanserin (5-125 ng/kg/min) were administered intra-arterially. The relative alpha 1-adrenergic receptor and 5-HT2 blocking potencies of ketanserin were investigated using intra-arterial infusions of cumulative doses of methoxamine (0.1, 0.3, and 0.5 microgram/kg/min), tyramine (0.25, 0.50, and 1.25 microgram/kg/min), and 5-HT (10, 30, and 80 ng/kg/min) together with a low dose (5 ng/kg/min) and a high dose (50 ng/kg/min) of ketanserin. Forearm blood flow was measured by venous occlusion plethysmography. Heart rate and intra-arterial blood pressure were recorded semicontinuously. Intra-arterial infusion of 5-HT induced an initial transient vasodilatation, followed by a steady vasodilatation for the low doses of 5-HT (0.1-10 ng/kg/min; p less than 0.05). A steady vasoconstriction was only obtained at the highest dose of 5-HT. Ketanserin induced a dose-dependent increase in forearm blood flow from 15 ng/kg/min (p less than 0.05) onward. The vasodilatation induced by 5-HT (1 ng/kg/min) was significantly enhanced by ketanserin (125 ng/kg/min; p less than 0.05), whereas the vasoconstriction elicited by 5-HT (80 ng/kg/min) was reversed by ketanserin (50 ng/kg/min; p less than 0.05), thus confirming that 5-HT2 receptors were stimulated by 5-HT.(ABSTRACT TRUNCATED AT 250 WORDS)
Single versus triplicate measurements of blood pressure and heart rate.
Authors: Fagan T C , Conrad K A , Mayshar P V , Mackie M J , Hagaman R M
Published: June 2012

The mean of rapidly repeated duplicate or triplicate measurements is often used in studies of antihypertensive drugs. Forty patients with hypertension had triplicate measurements of blood pressure and heart rate on two occasions, 1 week apart, during placebo treatment. The average difference between the first measurement and the mean of the triplicate measurements was -0.3 mm Hg. The average coefficient of variation for supine and standing, systolic and diastolic blood pressures was 8.4% for the single measurements and 8.0% for the mean of triplicate measurements. The correlations between the first measurements and the mean of triplicate measurements ranged from 0.90 to 0.98 (all p less than 0.01). The average difference between the two visits for all four blood pressure parameters was -0.6 mm Hg for the single measurements and -0.5 mm Hg for the mean of triplicate measurements (all p = NS). These results indicate that 1) blood pressure does not change further after 1 week of placebo treatment, and 2) use of the mean of triplicate measurements of blood pressure and heart rate gives the same result as use of single measurements, and the results are no less variable.
A higher cellular sodium turnover rate in cultured skin fibroblasts from blacks.
Authors: Kuriyama S , Hopp L , Tamura H , Lasker N , Aviv A
Published: June 2012

Differences in cellular Na+ and K+ regulation may relate to the pathogenesis of essential hypertension and the predisposition of blacks to this disease. To explore these tenets, we examined several aspects of cellular Na+ homeostasis in serially passed, cultured skin fibroblasts from 30 subjects (15 hypertensive blacks and whites and normotensive subjects matched for sex, age, and race.) Fibroblasts from blacks demonstrated higher cellular Na+ turnover rates than did those from whites. This difference was expressed by accelerated Na+-K+ pump activity (ouabain-sensitive Na+ washout rate, 3.46 +/- 0.216 for blacks vs 1.84 +/- 0.283 mEq/L/min for whites; p = 0.0006) and a higher rate of cellular accumulation of Na+ in the presence of ouabain (0.964 +/- 0.0743 vs 0.562 +/- 0.0440 mEq/L/min for blacks and whites, respectively; p = 0.0045). Associated with these findings, fibroblasts from blacks had higher cellular Na+ concentration than did those from whites (9.78 +/- 0.512 vs 7.50 +/- 0.400 mEq/L; p = 0.0170, as measured by atomic absorption, and 7.84 +/- 0.470 vs 5.03 +/- 0.980 mEq/L; p = 0.0141, as derived from the equilibrium distribution ratio of 22Na+). It is concluded that blacks differ from whites with respect to cellular Na+ turnover rate, which is evidenced by an increased Na+ influx and accelerated Na+-K+ pump activity in their fibroblasts. Our findings support the tenet that innate racial differences in cellular Na+ regulation may underlie the predisposition of blacks to hypertension.
Vascular and adrenal reninlike activity in chronically diabetic rats.
Authors: Ubeda M , Hernandez I , Fenoy F , Quesada T
Published: June 2012

The aim of this work was to investigate, in an experimental model of diabetes mellitus, the levels of renin activity in vascular and adrenal tissues and their relationship to several circulating renin-angiotensin system components. Rats with chronic (12 weeks) streptozocin-induced diabetes showed a significant decrease in plasma renin activity (PRA), plasma renin concentration, and plasma aldosterone. However, plasma trypsin activatable inactive renin concentration was increased (11.65 +/- 1.40 vs 6.73 +/- 0.57 ng angiotensin I/ml/hr; p less than 0.001), as were aortic reninlike activity (p less than 0.001) and adrenal renin, both in the zona glomerulosa (p less than 0.01) and the fascicular-reticular-medullary portion (p less than 0.001) with respect to an age-matched control group. After bilateral nephrectomy, plasma renin-angiotensin system components (PRA and plasma active and inactive renin concentrations) as well as aortic and fascicular-reticular-medullary renin activity significantly decreased in both control and diabetic rats. However, glomerular renin activity increased in control nephrectomized rats to the levels observed in diabetic animals but did not change in diabetic nephrectomized rats. The parallel changes of aortic and fascicular-reticular-medullary renin activity and plasma inactive renin concentration in diabetes and nephrectomy suggest an interdependent relationship, whereas the increase of glomerular renin activity in diabetic and nephrectomized animals, both with low levels of PRA, suggests the existence of a local autonomic renin-angiotensin system regulated by plasma feedback. Tissue renin-angiotensin system alterations in diabetes could mean that a pathogenic factor is involved in long-term diabetic complications or that only a compensatory physiological process is at work.
Direct effects of alpha 2-adrenergic receptor stimulation on intravascular systemic capacity in the dog.
Authors: Supple E W , Graham R M , Powell W J
Published: June 2012

The role of alpha 2-adrenergic receptor stimulation in the regulation of systemic vascular capacity and venous return, a major determinant of cardiac output, is not well understood. With the influence of the central nervous system isolated from the systemic circulation, the direct peripheral vascular effects of two specific, chemically distinct alpha 2-adrenergic receptor agonists, UK 14,304 and B-HT 920, were investigated in 19 dogs on total cardiopulmonary bypass with constant arterial perfusion and central venous pressure. Five-minute intra-arterial infusions of UK 14,304 (200 micrograms/min) resulted in increased arterial resistance (mean arterial pressure increased 18 +/- 4 [SEM] mm Hg; p less than 0.01) and a decrease in systemic vascular capacity (81 +/- 20 ml; p less than 0.01). This decrease in systemic vascular capacity appears to result from vasoconstriction, since there was no decrease in transhepatic resistance to portal flow and no significant change in hepatic vein flow to suggest redistribution of arterial blood flow. Yohimbine abolished both the arterial and systemic capacity effects, whereas prazosin did not. Intra-arterial administration of B-HT 920 (200 theta grams/min) in five dogs produced similar changes in arterial resistance and systemic capacity. These findings provide direct evidence for beta 2-adrenergic control, not only of arterial resistance but also of systemic vascular capacity, which in the intact animal would increase venous return to the heart.
Plasma kinin concentration in deoxycorticosterone-salt hypertension.
Authors: Nakagawa M , Nasjletti A
Published: June 2012

We investigated the status of circulating kinins in rats with severe hypertension caused by drinking 1% NaCl (saline) and treatment with deoxycorticosterone (DOC, 25 mg/kg/wk s.c.) for 5 weeks. Saline-drinking rats treated with DOC had a higher systolic blood pressure (210 +/- 4 mm Hg) than did rats without DOC treatment drinking water (138 +/- 3 mm Hg) or saline (141 +/- 3 mm Hg). The concentration of kinins in the inferior vena cava plasma of DOC-salt hypertensive rats did not differ from the venous plasma kinin concentration in normotensive rats drinking water or saline. In contrast, the arterial plasma kinin concentration in DOC-salt hypertensive rats (7.0 +/- 0.8 pg/ml) was lower (p less than 0.002) than that in water-drinking controls (14.0 +/- 2.2 pg/ml); it also was lower (p less than 0.005) in saline-drinking rats (8.1 +/- 0.9 pg/ml) than in water-drinking controls. Infusion of bradykinin (20 micrograms/kg/min i.v.) increased arterial plasma kinins in all the groups. Nonetheless, the arterial plasma kinin concentration achieved during bradykinin infusion in DOC-salt hypertensive (1590 +/- 130 pg/ml) and in saline-drinking rats (1540 +/- 100 pg/ml) was lower than that in water-drinking rats (2140 +/- 210 pg/ml). On the other hand, during infusion of the kininase II inhibitor captopril (80 micrograms/hr i.p.) for 3 days, neither DOC-salt hypertensive rats nor saline-drinking normotensive rats exhibited significant reduction of arterial plasma kinins relative to the level in water-drinking controls. These data indicate that high salt intake, irrespective of the level of blood pressure, causes the arterial plasma concentration of kinins to fall.(ABSTRACT TRUNCATED AT 250 WORDS)
Supernormal contractility in primary hypertension without left ventricular hypertrophy.
Authors: de Simone G , Di Lorenzo L , Costantino G , Moccia D , Buonissimo S , de Divitiis O
Published: June 2012

Forty-three subjects with uncomplicated primary hypertension and without echocardiographic left ventricular hypertrophy and 54 normotensive volunteers were studied by two-dimensional targeted M-mode echocardiography to evaluate systolic function and contractility before the development of compensatory hypertrophy. The ratio of peak systolic pressure to end-systolic dimension was used to assess left ventricular performance and was divided for either posterior wall thickness or cross-sectional area to generate hypertrophy-independent indices of inotropic state. Fractional shortening was normal in the hypertensive group, despite the increase in end-systolic stress. Systolic pressure/dimension ratio was higher in hypertensive subjects (p less than 0.001), as were hypertrophy-independent indices of inotropic state (p less than 0.005), which were inversely correlated to left ventricular mass (p less than 0.001). Values in 11 hypertensive subjects were above the upper confidence limit of the normal shortening/stress relation, which provides a load-independent measure of inotropic state. They showed high hypertrophy-independent indices of inotropic state (p less than 0.01), while the other hypertensive subjects did not. High fractional shortening, wall stress, and systolic pressure (p less than 0.01) were found in the subgroup with supernormal performance, while left ventricular mass was not different from that of other subgroups, depicting inadequate left ventricular hypertrophy. The duration of hypertension was the same in the subgroups. Supernormal inotropic state could be considered one form of primary adaptation to high wall stress that serves to maintain systolic ventricular performance.
Diltiazem and left ventricular hypertrophy in renovascular hypertensive rats.
Authors: Grellet J P , Bonoron-Adèle S M , Tariosse L J , Besse P J
Published: June 2012

The effects of diltiazem treatment (40-50 mg/kg/day orally for 8 weeks) of left ventricular hypertrophy on systemic and coronary hemodynamics and mechanical cardiac performance were investigated in renovascular hypertensive rats (Goldblatt, two-kidney, one clip). Systemic and coronary hemodynamics were determined by using radioactive microspheres in conscious, unrestrained rats. Mechanical performance was measured on isolated papillary muscle from the same animal. Nine treated hypertensive rats were compared with control groups: 12 untreated hypertensive and nine sham-operated rats. Diltiazem treatment led to an effective but incomplete control of blood pressure (from 208 +/- 5 mm Hg in the untreated hypertensive group to 155 +/- 3 mm Hg in the treated hypertensive group; p less than 0.01) associated with a significant but incomplete decrease of the left ventricular mass (from 3.10 +/- 0.19 mg/g in untreated hypertensive rats to 2.35 +/- 0.04 mg/g in treated hypertensive rats; p less than 0.01). A close correlation was found between left ventricular mass and systolic blood pressure in untreated, treated, and pooled groups (r = 0.84, p less than 0.001, n = 30). The left ventricular weight to systolic blood pressure ratio was equivalent in all three groups, so that the reduction of left ventricular mass in diltiazem-treated rats was commensurate with the reduction of blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)