bluuebunny/crossref_metadata_2025 huggingface dataset:
Endothelin-1 and Its mRNA in the Wall Layers of Human Arteries Ex Vivo
Authors: Rossi Gian Paolo , Colonna Stefania , Pavan Edoardo , Albertin Giovanna , Della Rocca Foscarina , Gerosa Gino , Casarotto Dino , Sartore Saverio , Pauletto Paolo , Pessina Achille C.
Published: June 2012

Background
—The participation of endothelin-1 (ET-1) in the control of vascular tone in humans has been questioned, on the basis of the finding of subthreshold immunoreactive (ir) ET-1 plasma levels. However, because most ET-1 is secreted abluminally, it might attain a higher concentration in the tunica media than in plasma. Furthermore, evidence indicates that vascular smooth muscle cells (VSMCs) can synthesize ET-1 on stimulation in vitro. We therefore looked for irET-1 in the different layers of the wall of human arteries, including renal, gastric, and internal thoracic artery wall, obtained ex vivo from consenting patients with coronary artery disease and/or high blood pressure undergoing surgery, as well as from young organ donors.

Methods and Results
—We performed immunohistochemistry with specific anti–ET-1 and anti-vWF antibodies followed by detection with an avidin-biotin complex ultrasensitive kit. The presence of preproET-1 and human endothelin-converting enzyme-1 (hECE-1) mRNA was also investigated by reverse transcription–polymerase chain reaction in homogenates of vessel wall, including preparations deprived of both endothelium and adventitia, and in isolated VSMCs. We detected irET-1 in the endothelium of all arteries and in the tunica media of internal thoracic artery from most patients with coronary artery disease. PreproET-1 and hECE-1 mRNA was also detected in VSMCs isolated from these vessels. irET-1 and irvWF staining in endothelium and tunica media was measured by use of microscope-coupled computer-assisted technology. Significant correlations between the amount of irET-1 in the tunica media and mean blood pressure (
P
<0.05), total serum cholesterol (
P
<0.05), and number of atherosclerotic sites (
P
<0.001) were found. Thus, in organ donors, irET-1 was detectable almost exclusively in endothelial cells, whereas in patients with coronary artery disease and/or arterial hypertension, sizable amounts of irET-1 were detectable in the tunica media of different types of arteries. In addition, VSMCs isolated from these vessels coexpressed the preproET-1 and hECE-1 genes.

Conclusions
—Collectively, these findings are consistent with the contention that endothelial damage occurs in most patients with atherosclerosis and/or hypertension and that ET-1 is synthesized in VSMCs of these patients.
Converting enzyme inhibition in essential hypertension: the hypotensive response does not reflect only reduced angiotensin II formation.
Authors: Swartz S L , Williams G H , Hollenberg N K , Moore T J , Dluhy R G
Published: June 2012

To determine the relative importance of hormonal factors in mediating the hypotensive response to converting enzyme inhibition (CEI), plasma renin activity (PRA), angiotensin II, and bradykinin responses to SQ20,881 were measured in 20 supine patients with essential hypertension in balance on a 10 mEq sodium diet. Patients were divided into two groups according to their diastolic blood pressure response: responders had a decrement in diastolic pressure which exceeded 9 mm Hg, the upper value of the 95% confidence limits for normotensive patients studied under similar conditions; nonresponders did not. Compared to the nonresponders, responders not only had a higher control PRA (8.7 +/- 1.7 ng/ml/hr vs 4.8 +/- 2.1, p < 0.05) and larger decrement in plasma angiotensin II (18.7 +/- 4.9 pg/ml vs 3.2 +/- 1.7, p < 0.01), but also had a higher control bradykinin (3.2 +/- 0.7 ng/ml vs 1.1 +/- 0.2, p < 0.05) and larger increment in bradykinin (4.5 +/- 1.3 ng/ml vs 1.0 +/- 0.4, p < 0.05) following SQ20,881. Because SQ20,881 altered both angiotensin II and bradykinin concentrations, we assessed the contribution of blockade of angiotensin II formation by administering angiotensin II infusions to seven responders during coverting enzyme blockade, with the angiotensin II dose adjusted to restore diastolic pressure to control levels. The plasma angiotensin II level required to return blood pressure to control was 45 +/- 15 pg/ml higher than the control plasma angiotensin II level (p < 0.01), suggesting that some other factor(s), perhaps bradykinin, are also responsible for the hypotensive response to converting enzyme inhibition.
The substitutive role of ACTH in supporting aldosterone response to head-up tilt during acute renin suppression in patients with essential hypertension.
Authors: Morganti A , Sealey J E , Lopez-Ovejero J A , Pickering T G , Laragh J H
Published: June 2012

The relative contribution of the renin-angiotensin system, adenocorticotrophic hormone (ACTH) and plasma electrolytes in the response of plasma aldosterone to 30 minutes of 65 degrees head-up tilt was assessed in 10 essential hypertensive patients. Studies were carried out before and during acute blockade of renin release by propranolol, ACTH suppression by dexamethasone and combined renin and ACTH blockade. In control studies orthostasis induced significant increases only in plasma renin activity and aldosterone. In contrast, when the renin response to tilt was acutely suppressed by propranolol administration, the aldosterone response was nonetheless maintained but now appeared to be under ACTH control, since concurrent increases in cortisol were observed. During ACTH suppression aldosterone increased during tilt and so did renin. However, during combined ACTH and renin blockade aldosterone failed to increase during tilt. These studies suggest that the aldosterone secretory response to head-up tilt is normally mediated by the renin-angiotensin system but, when the renin response is suppressed, an ACTH response is elicited which assumes a backup role. However, when these two systems are blocked other factors appear unable to respond during tilt to support a normal aldosterone response.
Circadian changes in plasma renin activity and plasma aldosterone concentration in two-kidney hypertension rats.
Authors: DeForrest J M , Davis J O , Freeman R H , Stephens G A , Watkins B E
Published: June 2012

Circadian changes in plasma renin activity (PRA) and plasma aldosterone concentration (PAC) in normal and hypertensive rats were determined by measurements at 8 a.m., 4 p.m. and 12 midnight (MN). For the normals, PRA and PAC were highest at 4 p.m. Animals made hypertensive by constriction one renal artery with the other kidney intact were studied after 4, 5, 7 and 10 weeks; the clear-cut circadian rhythm for PRA in normals had disappeared but for PAC the circadian rhythm was present in the 4-, 5- and 10-week groups. Both PRA and PAC were elevated in all four hypertensive groups compared with the normal controls and there was a highly significant correlation between PRA and PAC. The 4 p.m. peak value for PAC was much higher in relation to the 8 a.m. and 12 MN values values in the hypertensive animals than in the normals. Sodium balance studies failed to demonstrate any appreciable differences among the groups. When the hypertensive animals were divided into two groups on the basis of the level of hypertension, the rats with moderate hypertension showed an average elevation in PRA which was significant in only the 4- and 7-week groups whereas PRA was elevated in all four groups with severe hypertension. Thus, the present data help to define the activity of the renin-angiotensin-aldosterone system in two-kidney, one clip hypertension in the rat.
Serial renin-angiotensin studies in spontaneously hypertensive and Wistar-Kyoto normotensive rats. Transition from normal- to high-renin status during the established phase of spontaneous hypertension.
Authors: Bagby S P , McDonald W J , Mass R D
Published: June 2012

To characterize the renin-angiotensin system in the Aoki-Okamoto spontaneously hypertensive rat (SHR) more fully, serial measurements of plasma renin activity (PRA), plasma renin concentration (PRC), renin reactivity (as relative index of circulating modifiers of the renin reaction) and renin substrate concentration were made in 6- to 64-week-old SHR and in age-matched Wistar-Kyoto normotensive rats (WKY). In the evolving phase of SHR hypertension (6 and 13 weeks of age), PRA was comparable to WKY control values, whereas mature SHR with established hypertension developed, between 13 and 35 weeks of age, a high-PRA state persisting through 64 weeks of age. In 64-week-old SHR, increased plasma volume (3.54 +/- 0.91 in SHR vs. 3.18 +/- 0.90 ml/100 g body weight in WKY, p less than 0.025), together with increased PRA (24.9 +/- 3.8 in SHR vs. 13.1 2.2 ng AI/ml plasma/hr in WKY, p less than 0.025), suggest that volume decrease cannot explain increased PRA. In 42-week-old SHR, PRA was incompletely suppressed by deoxycorticosterone acetate plus 1% saline orally for 4 days: 4.9 +/- 1.2 in SHR vs. 0.6 +/- 0.8 ng angiotensin I/ml plasma/hr in WKY, p less than 0.001. Modestly increased renin reactivity of plasma was observed in SHR at all ages studied, supporting the ubiquity of increased circulating accelerators (or decreased inhibitors) of the renin reaction in hypertensive states. However, elevated renin reactivity did not account for the transition from normal to high PRA observed in mature SHR, nor did renin substrate concentration, which was consistently lower in SHR than in age-matched WKY. Temporal patterns of, and strain differences in PRA were closely paralleled by variations in PRC but not by other reaction components. Significant elevation of serum creatinine in old SHR support the presence of renal injury. We conclude that PRA and PRC are normal in evolving SHR hypertension and progress to abnormally elevated levels after hypertension is established. We postulate that "high-renin" hypertension may develop as a consequence of the hypertensive state per se, perhaps due to nephrosclerotic vascular disease.
Clonidine and carotid baroreflex in essential hypertension.
Authors: Mancia G , Ferrari A , Gregorini L , Zanchetti A
Published: June 2012

Clonidine is believed to reduce blood pressure by a neural action and animal experiments suggest that this consists in potentiation of baroreflexes. In 16 patients with essential hypertension we studied the effects of alterations in carotid sinus baroreceptor activity (neck chamber technique) on arterial blood pressure (catheter measurements) and heart rate, before and after intravenous administration of 150 microgram and 300 microgram of clonidine. The magnitude of the reflex responses was assessed by the slope of the linear regressions relating applied increase and decrease in tissue pressure at the carotid sinus (and therefore applied decrease and increase in carotid sinus transmural pressure) and resulting changes in mean arterial pressure and R-R interval. Clonidine caused a marked reduction in mean arterial pressure (-26 +/- 3 mm Hg) and a slight but significant reduction in heart rate (-5 +/- 1 b/min). There was no evidence for a potentiation of the baroreceptor influence on blood pressure, although a slight potentiation of the baroreceptor influence on heart rate was observed in few instances. We conclude that in man clonidine can exert a pronounced hypotensive effect without potentiating baroreceptor influence on blood pressure. Therefore this mechanism does not play a prominent role in the clinical antihypertensive action of the drug.
Glomerular and renal hemodynamics during converting enzyme inhibition (SQ20,881) in the dog.
Authors: Navar L G , LaGrange R A , Bell P D , Thomas C E , Ploth D W
Published: June 2012

It has been suggested that intrarenal levels of angiotensin II may preferentially control efferent arteriolar resistance or may influence the glomerular filtration coefficient (Kf). To examine these possibilities, micropuncture and clearance experiments were performed on nine anesthetized dogs evaluating renal and glomerular hemodynamics before and during the administration of an angiotensin converting enzyme inhibitor (SQ20,881). During the micropuncture measurements, renal arterial pressure was reduced to range of 85 to 90 mm Hg in order to maximize renin secretion and intrarenal formation of angiotensin II. Also, this procedure minimizes potential errors in the determination of single nephron glomerular filtration rate (SNGFR) and of glomerular pressure when estimated by techniques that require complete blockade of proximal tubule fluid flow. During the administration of SQ20,881, a converting enzyme inhibitor (CEI), renal blood flow increased significantly by 13%, but GFR was not altered. There were no significant alterations in SNGFR, proximal tubule pressure, peritubular capillary pressure or estimated glomerular pressure. By using the micropressure measurements in combination with the whole kidney hemodynamic data, it was estimated that afferent resistance was reduced 23%. Although significant decreases in efferent resistance could not be documented, there was a tendency for this variable to decrease also. Neither Kf nor effective filtration pressure were altered significantly by CEI. These results do not support the contention that intrarenal effects of angiotensin II are exerted predominantly on the efferent arteriolar resistance segments; rather, they suggest that angiotensin may exert a modest tonic effect on both pre- and postglomerular resistance elements in the anesthetized hydropenic dog.
Role of renin-angiotensin system in chronic renal hypertensive rats.
Authors: Sen S , Smeby R R , Bumpus F M , Turcotte J G
Published: June 2012

The role of renin-angiotensin system has been examined in the maintenance of hypertension in acute and chronic two-kidney (36 weeks) and chronic one-kidney (12 weeks) Goldblatt hypertensive rats using three inhibitors of this system. The inhibitors used were URI-73A, a synthetic analog of lysophosphatidylethanolamine, which inhibits renin both in vivo and in vitro, SQ14,225, a potent converting enzyme inhibitor, and [Sar1, Thr8] angiotensin II, an angiotensin II antagonist. When the inhibitors were administered in acute (high renin) hypertensive rats, they all lowered blood pressure significantly. However, in the chronic (low renin) hypertensive phase, both renin and converting enzyme inhibitors lowered blood pressure, whereas, Sar1, Thr8 failed to lower blood pressure. The renin inhibitor lowered plasma renin activity (PRA), and SQ14,225 and [Sar1, Thr8] Ang II increased PRA. Further studies on water and electrolyte balance with one-kidney model hypertensive and uninephrectomized control rats showed no change in plasma volume. However, there was increased 24-hour urinary output and increased sodium excretion. This study indicates that in chronic renal hypertensive rats, blood pressure reduction is possible by either renin on converting enzyme inhibitor, but not by angiotensin antagonists. Since volume did not change either during the development or reversal of hypertension, volume did not appear to play a major role in the maintenance of hypertension.
Association of blood groups with essential and secondary hypertension. A possible association of the MNS system.
Authors: Miller J Z , Grim C E , Conneally P M , Weinberger M H
Published: June 2012

Persons participating in a 5-day diagnostic protocol were routinely typed for ABO, Rh, MNS, Kell, Kidd, Duffy, P, Haptoglobin, phosphoglucomutase-1 (PGM-1), and acid phosphatase (AcP). The study population was composed of 164 normotensive whites, 34 normotensive blacks, 161 whites and 43 blacks with essential hypertension, and 52 whites with secondary forms of hypertension (18 atherosclerotic renovascular hypertensives, 17 patients with fibromuscular disease, and 17 patients with primary aldosteronism). There were no significant differences in phenotype frequencies in ABO, Rh, Kidd, Kell, Duffy, P, Haptoglobin, PGM-1 or AcP in any of the comparisons. However, there was a significantly different distribution of MNS phenotypes in comparisons of essential and atherosclerotic renovascular hypertensives with normotensive controls. Essential hypertensives had a lower frequency of the S gene and a higher frequency of s in whites (X2 = 12.21, p less than 0.005). Atherosclerotic renovascular hypertensives differed from the normotensive population in the frequencies of both MN (X 2 = 4.34, p less than 0.05) and Ss (X2 = 4.21, p less than 0.05). The finding of disease-blood group associations supports the hypothesis that there may be significant physiological differences between individuals of different blood types.
Changes in renal vascular sensitivity and arterial pressure associated with sodium intake during long-term intrarenal norepinephrine infusion in dogs.
Authors: Cowley A W , Lohmeier T E
Published: June 2012

Experiments were performed on conscious uninephrectomized dogs to determine the comparative effects of chronic intrarenal and intravenous norephrine (NE) infusion (0.27 microgram/kg/min) on the steady-state values for arterial pressure, plasma renin activity (PRA), and renal function at four levels of sodium intake (5, 40, 120 and 240 mEq/day). Arterial pressure was monitored continuously 24 hr/day with on-line computer techniques. Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and plasma renin activity (PRA) were determined after sodium and water balance was achieved. During intrarenal NE infusion, ERPF and GFR decreased progressively from 15% to 30% and from 24% to 46% respectively, while renal vascular resistance increased progressively from 40% to 140% as sodium intake was increased from 10 to 240 mEq/day. Both ERPF and renal resistance, but not GFR, returned to control levels during intravenous NE infusion at each level of sodium intake and after terminating NE infusion. During intrarenal NE infusion the steady-state value for mean arterial pressure increased from a control of 105 to 118 mm Hg when the sodium intake was 10 mEq/day. Pressure then increased progressively from 118 to 135 mm Hg as the sodium intake was elevated from 10 to 240 mEq/day. Increases in arterial pressure associated with intravenous NE infusion were significantly smaller at each sodium level than those achieved with intrarenal NE infusion. At each level of sodium intake, PRA was elevated during intrarenal NE infusion and returned to control after NE infusion. Intravenous NE infusion did not increase PRA above control levels. The data are compatible with the concept that enhanced renal adrenergic activity could initiate and sustain hypertension chronically by basic alterations in renal function.
Serum immunoglobulins in hypertension.
Authors: Adlin E V , Moctezuma J , Marks A D , Moctezuma J , Channick B J
Published: June 2012

We measured serum immunoglobulins in 52 persons whose blood pressure was higher than 140/90 mm Hg, and 52 normotensive controls matched for age, sex and race. All were selected from a population of actively employed persons undergoing a routine health evaluation. Contrary to previous reports, the hypertensive subjects did not have higher levels of IgG or IgA than the controls. Sixteen hypertensive subjects with mean blood pressure higher than 115 mm Hg did not have elevated IgG or IgA levels when analyzed separately. Serum IgM was significantly lower in the 52 hypertensive subjects (125 +/- 67 mg/dl vs 171 +/- 85 mg/dl, p less than 0.01). Our subjects failed to show the increase in immunoglobulins reported by others. The most likely reasons for this is the mildness of their blood pressure elevation, although the absence of immunoglobulin elevation in the small number with more marked hypertension does not support this explanation.
Arteriolar reactivity to pressure stimuli in hamsters with renal hypertension.
Authors: Stacy D L , Joyner W L , Gilmore J P
Published: June 2012

The responses to alterations in extravascular pressure were studied in five orders of arterioles in the cheek pouch of normotensive and renal hypertensive hamsters. Renal hypertension was induced by bilateral compression of both kidneys using figure-of-eight ligatures. Ten to 16 days later, hamsters were anesthetized with pentobarbital (6.0 mg/100 g body weight) and a Plexiglas chamber was positioned in the cheek pouch. Chamber pressure, or extravascular pressure, was increased and decreased by +/- 10, 20, and 40 mm Hg, and arteriolar diameters were monitored continuously. The responses at -20 mm Hg and the slope of the linear portion of the chamber pressure-diameter curve (arteriolar gains) were compared between groups for each branching order of arteriole. Arteriolar responses at one chamber pressure and the arteriolar gains were enhanced in third and fourth order arterioles of the renal hypertensive group compared with the normotensive group, and the responses of these small arterioles were greater than those of larger arterioles in both groups. Control diameters of second and third order arterioles were significantly smaller in the renal hypertensive group, while the diameters after adenosine were not different. These results suggest that the enhanced responses of small arterioles in the renal hypertensive group were not related to structural alterations but may be related to an increased reactivity of smooth muscles in these small arterioles to volume expansion, thus a pressure stimulus.
Multiple effects of calcium entry blockers on renal function in hypertension.
Authors: Romero J C , Raij L , Granger J P , Ruilope L M , Rodicio J L
Published: June 2012

Characterization of the renal effects of calcium entry blockers has not been easy because the inhibition of Ca2+ cellular influx alters several regulatory functions. The ability of calcium blockers to dilate renal vasculature and to increase glomerular filtration rate is largely determined by the preexisting vascular tone. However, the increments in sodium excretion could occur without alterations in renal hemodynamics. Calcium blockers could increase sodium excretion by inducing a redistribution of renal blood flow toward juxtamedullary nephrons, by inhibiting tubuloglomerular feedback responses, or by a direct action on the tubular transport of sodium. These effects are poorly understood at present. In vitro studies show that the blockade of calcium entry enhances renin secretion and decreases prostaglandin synthesis. This dissociation has not been found during long-term administration, which has been proved to be effective for the treatment of essential hypertension with normal maintenance of renal function. In this respect, there are reports indicating that calcium blockers are particularly effective in a subgroup of patients with essential hypertension who exhibit subtle but detectable alterations in calcium metabolism. Further studies are needed to determine whether this significant response to calcium blockers is due to correction of an early defect of calcium cellular kinetics that initiated the increase in blood pressure.
Effects of volume change on circulating immunoreactive atrial natriuretic factor in rats.
Authors: Kohno M , Clegg K B , Sambhi M P
Published: June 2012

The mammalian atrial hormone atrial natriuretic factor (ANF) has been shown to have potent natriuretic and diuretic actions as well as vasodilator effects when released into the circulation. To investigate how the levels of the circulating form of this peptide change with alteration of intravascular fluid volume, we measured immunoreactive ANF in the plasma of Wistar rats after acute saline load, acute furosemide treatment, and chronic water restriction. Circulating levels of immunoreactive ANF increased significantly (p less than 0.001) 1 minute after acute saline load and returned to normal levels within 5 minutes. Volume contraction induced by furosemide treatment of chronic water restriction significantly reduced the circulating immunoreactive ANF. These data indicate that acute volume expansion causes an immediate release of immunoreactive ANF into the general circulation and acute volume contraction results in a decline of circulating levels of immunoreactive ANF, which is maintained during chronic volume contraction. These results suggest that the atria detect alterations in intravascular fluid volume and respond by changing the levels of ANF acutely as well as chronically and thereby participate in the regulation of body fluids and, perhaps, of blood pressure.
Furosemide augments the effects of captopril on nuclear studies in renovascular stenosis.
Authors: Kopecky R T , Thomas F D , McAfee J G
Published: June 2012

Captopril facilitates detection of unilateral renovascular hypertension by selectively reducing glomerular filtration rate in affected kidneys. To determine if volume depletion augments this response, we compared the effects of captopril, furosemide, and combined furosemide plus captopril on individual kidney computer-derived clearances of 99mTc-diethylenetriamine pentaacetic acid (DTPA) and [131I]o-iodohippurate in two-kidney, one clip Goldblatt hypertensive rats and normal controls. In clipped kidneys, captopril reduced DTPA clearance significantly from baseline (from 0.31 +/- 0.02 to 0.19 +/- 0.04 ml/min/100 g; p less than 0.02) whereas furosemide alone had no effect (0.28 +/- 0.03 ml/min/100 g). Combined furosemide plus captopril further reduced clipped kidney DTPA clearance to a level significantly less than captopril alone (0.10 +/- 0.02 ml/min/100 g; p less than 0.02). Clipped kidney o-iodohippurate clearance was not changed from baseline by any treatment. In contralateral unclipped and normal kidneys, DTPA clearance did not decline from baseline following either captopril or furosemide plus captopril treatment. Since the dose of captopril used (3 mg/kg by intraperitoneal injection) did not reduce systolic blood pressure of hypertensive rats significantly, these changes probably reflect intrarenal rather than systemic hemodynamic effects of converting enzyme inhibition and are consistent with the hypothesis that captopril interferes with glomerular filtration in stenotic kidneys by reducing efferent arteriolar vascular resistance. Prior volume depletion accentuates the effect of captopril on stenotic kidney glomerular filtration rate, providing improved functional discrimination of stenotic kidneys from contralateral unclipped and normal kidneys. These results indicate that furosemide-induced volume depletion may increase the diagnostic sensitivity of captopril-enhanced 99mTc-DTPA renography in the detection of unilateral renovascular hypertension.
Progress in the battle against hypertension. Changes in blood pressure levels in the United States from 1960 to 1980.
Authors: Dannenberg A L , Drizd T , Horan M J , Haynes S G , Leaverton P E
Published: June 2012

Intensive efforts by practicing physicians and public health workers to identify and treat persons with hypertension have been underway for many years. In this report, changes in blood pressure levels in the United States are assessed based on nationally representative health (and nutrition) examination surveys conducted by the National Center for Health Statistics in 1960 to 1962, 1971 to 1974, and 1976 to 1980. Analysis of age-adjusted data for adults aged 18 to 74 years (including those on antihypertensive medication) indicates that between the first and third surveys for whites and blacks, respectively, mean systolic blood pressure declined 5 and 10 mm Hg; the proportion of persons with systolic blood pressure of 140 mm Hg or higher fell 18 and 31%; the proportion with undiagnosed hypertension decreased 17 and 59%; and the proportion taking antihypertensive medications rose 71 and 31%. These differences between the first and third surveys were all statistically significant (p less than 0.05 or better). Changes in diastolic blood pressure levels were generally not significant among race-sex groups. The proportion of persons with definite hypertension (i.e., systolic blood pressure greater than or equal to 160 mm Hg, and/or diastolic blood pressure greater than or equal to 95 mm Hg, and/or taking antihypertensive medication) declined among blacks but rose slightly among whites. Study results are consistent with the recent decline in cardiovascular disease mortality.
Effect of sodium balance and calcium channel blocking drugs on blood pressure responses.
Authors: Anderson G H , Howland T , Domescek R , Streeten D H
Published: June 2012

To study the role of calcium movements in mediating the effects of sodium chloride on the response of blood pressure to angiotensin II (ANG II), we infused ANG II before and after giving calcium channel blocking drugs (nifedipine and diltiazem) and calcium infusions to normal subjects during high and low sodium intakes. ANG II was also in nine patients with essential hypertension eating a low sodium diet. In preliminary studies, the effects of nifedipine, 20 mg p.o., on blood pressure and plasma renin activity were determined. Sensitivity to infused ANG II was calculated as the slope of the linear regression of the increase in diastolic blood pressure (DBP) expressed as a function of the ANG II infusion rate (mm Hg/ng ANG II/kg/min). During intake of a high sodium diet (Na, 200 mEq/day) both drugs significantly (p less than 0.05) reduced ANG II sensitivity, while on a low sodium diet (10 mEq Na), neither drug reduced ANG II sensitivity. There was a significant (p less than 0.001) inverse correlation between the initial ANG II-DBP sensitivity and the change in sensitivity induced by the calcium channel blocking drugs in normal subjects (r = -0.78) and in hypertensive patients (r = -0.70). Five hypertensive patients had greater than normal ANG II-DBP sensitivity that was significantly (p less than 0.05) reduced by nifedipine. Calcium infusion did not affect the ANG II-DBP sensitivity on either diet. The results suggest that in normal subjects increased DBP responses to ANG II, induced by an increase in sodium intake, are partially mediated by increased extracellular to intracellular calcium movements, since they are blocked by the structurally different calcium channel blocking drugs nifedipine and diltiazem. In hypertensive patients on a low sodium diet, increased DBP responses to ANG II infusion were blocked by nifedipine, indicating they are at least partly mediated by increased extracellular to intracellular calcium flux.
Role of nisoldipine on blood pressure, cardiac hypertrophy, and atrial natriuretic peptides in spontaneously hypertensive rats.
Authors: Stasch J P , Kazda S , Hirth C , Morich F
Published: June 2012

The effect of long-term treatment with the calcium antagonist nisoldipine on development of hypertension, cardiac hypertrophy, and plasma levels of atrial natriuretic peptides (ANP) was determined in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) of the same age. Measurement of immunoreactive ANP in plasma provided a sensitive marker for the severity of hypertension and the associated cardiac overload. Long-term treatment with nisoldipine prevented the development of hypertension, the associated heart failure, and the increase of plasma levels of ANP in SHR but had no effect on systolic blood pressure, heart weight, and plasma levels of ANP in WKY. In addition, nisoldipine had a therapeutic effect in old SHR with manifest cardiac failure in end-stage hypertension, as evidenced not only by the reduction of blood pressure but also by the reduction of cardiac hypertrophy, of elevated immunoreactive ANP in plasma, and of increased plasma renin activity.
Hypotensive and bradycardic effects of centrally administered vasopressin in stroke-prone spontaneously hypertensive rats.
Authors: Imai Y , Abe K , Sasaki S , Minami N , Nobunaga T , Sekino H , Yoshinaga K
Published: June 2012

The cardiovascular effects of centrally administered arginine vasopressin were studied in stroke-prone spontaneously hypertensive rats and Wistar-Kyoto rats. Arginine vasopressin was infused intracerebroventricularly into conscious rats at a rate of 2 pg/kg/min (4.6 microliter/hr) for 21 hours, and blood pressure and heart rate were monitored. Arginine vasopressin caused transient hypertension and tachycardia in Wistar-Kyoto rats, whereas it induced delayed hypotension and bradycardia in stroke-prone spontaneously hypertensive rats. The effects on the latter lasted for 24 to 72 hours after cessation of the infusion. Intravenous administration of arginine vasopressin at a rate of 2 pg/kg/min did not cause any change in blood pressure and heart rate in these rats. These results suggest that arginine vasopressin acts centrally to depress cardiovascular activities, at least in stroke-prone spontaneously hypertensive rats.
Oral calcium treatment lowers blood pressure in renovascular hypertensive rats by suppressing the renin-angiotensin system.
Authors: Kageyama Y , Suzuki H , Arima K , Saruta T
Published: June 2012

The effects of calcium supplementation on blood pressure and its mechanisms were investigated in two-kidney, one clip renovascular hypertensive rats. Two series of experiments were performed: one was begun just after renal artery constriction, the other after the onset of hypertension. Calcium supplementation significantly attenuated the development of hypertension (systolic blood pressure: 183 +/- 8 vs 130 +/- 2 mm Hg) and was found to abate existing renovascular hypertension (systolic blood pressure: from 183 +/- 8 to 151 +/- 4 mm Hg). Calcium treatment did not cause significant alterations in fluid intake, urine volume, or urinary sodium excretion in either study. However, increased plasma renin activity and plasma aldosterone concentration were suppressed to the basal levels at the end of 3 weeks of calcium treatment (14 +/- 3 vs 8 +/- 2 ng angiotensin I/ml/hr; 530 +/- 50 vs 380 +/- 40 pg/ml). Blood pressure of calcium-treated renovascular hypertensive rats responded poorly to blockade of the renin-angiotensin system with captopril injection and angiotensin II analogue (saralasin) infusion. Further, in rats with chronic established renovascular hypertension, calcium treatment attenuated the enhanced pressor response to norepinephrine, but not to angiotensin II. These results suggest that the blood pressure-lowering actions of calcium supplementation are related primarily to suppression of renin secretion and secondarily to alteration of pressor response to norepinephrine in two-kidney, one clip renovascular hypertensive rats.
Role of prostaglandins and kinins in the renal pressor reflex.
Authors: Faber J E
Published: June 2012

In previous studies we identified an afferent renal nerve-dependent pressor reflex elicited by acute unilateral renal artery stenosis (50% decrease in renal blood flow) in conscious, instrumented rats with reduced responsiveness of arterial baroreceptor reflexes and the renin-angiotensin system. The pressor reflex involves a neurogenic increase in peripheral resistance. The present study examined the nature of the intrarenal stimulus underlying this renal pressor reflex. Rats were subjected to sinoaortic denervation and, 7 to 10 days later, were chronically instrumented with Doppler flow probes on the right renal artery, superior mesenteric artery, and abdominal aorta and with an occluder on the right renal artery. Following surgical recovery and inhibition of the renin-angiotensin system (captopril), animals received intravenous isotonic saline, 6% of body weight over 60 minutes. Saline infusion did not alter baseline hemodynamics, vascular neurogenic tone, or responsiveness to tyramine, but it attenuated the reflex by 70%. A second series of experiments examined a possible role for intrarenal prostaglandins, kinins, or adenosine in the activation of renal sensory receptors during renal stenosis. Prostaglandin inhibition with intravenous administration of indomethacin and meclofenamate virtually abolished the reflex in the face of enhanced tyramine responsiveness, whereas kallikrein inhibition (aprotinin) attenuated the reflex pressor response by 33%. Adenosine inhibition with aminophylline or adenosine deaminase had no effect on the reflex; these agents and aprotinin did not affect vascular neuroeffector responsiveness (tyramine). The data suggest that the renal pressor reflex may be mediated by renal sensory nerves, possibly chemoreceptors, whose activation could depend on renal excretory function and synthesis of prostaglandins and kinins.
Impaired control of vasopressin release in hypertensive subjects with cardiac hypertrophy.
Authors: Trimarco B , De Luca N , De Simone A , Volpe M , Ricciardelli B , Lembo G , Condorelli M
Published: June 2012

The effects of graded lower body negative pressure (-10 and -40 mm Hg) on vascular resistance and plasma vasopressin, norepinephrine, and renin activity were assessed in seven hypertensive subjects with left ventricular hypertrophy and seven sex-matched and age-matched normotensive subjects. In both groups increasing levels of lower body negative pressure induced a progressive decrease in right atrial pressure and an increase in vascular resistance. In normal subjects plasma vasopressin, norepinephrine, and renin activity were progressively raised, whereas only the higher level of stimulation increased plasma renin activity, norepinephrine, and vasopressin in hypertensive subjects. Propranolol induced a significant increase in plasma vasopressin in normal subjects (from 1.3 +/- 0.1 to 2.0 +/- 0.1 pg/ml; p less than 0.05) but not in hypertensive subjects. In this latter condition -10 mm Hg lower body negative pressure failed to increase plasma vasopressin, norepinephrine, and renin activity in normal subjects. Propranolol abolished the change in plasma renin activity in both groups, reduced the increase in vascular resistance induced by -40 mm Hg lower body negative pressure in normotensive subjects, but did not modify the rise in vasopressin elicited by this stimulus in normal subjects or the humoral and hemodynamic reflex responses evoked in hypertensive subjects. These results suggest that cardiopulmonary receptors are involved in the control of vasopressin release in normal subjects, whereas in hypertensive subjects with left ventricular hypertrophy, this control is altered because of an impaired function of cardiopulmonary receptors.
Effect of angiotensin II on baroreceptor reflex control of heart rate in conscious baboons.
Authors: Garner M G , Phippard A F , Fletcher P J , Maclean J M , Duggin G G , Horvath J S , Tiller D J
Published: June 2012

Studies of the baroreceptor-heart rate reflex were performed in four conscious, unrestrained male baboons to determine whether changes in circulating angiotensin II within the physiological range are associated with alterations in baroreceptor reflex sensitivity. With the animals on a high sodium intake, studies were performed before and during graded angiotensin II infusion (10 and 20 ng/kg/min). To separate effects on baroreceptor reflex function mediated by angiotensin II-induced increases in arterial pressure, these studies were repeated on a different day with simultaneous glyceryl trinitrate infusion to prevent increases in pressure during angiotensin II infusion. With the animals on a low sodium intake, studies were performed before and after angiotensin converting enzyme inhibition with captopril (1 and 5 mg/kg). These studies were also repeated on a separate day during simultaneous phenylephrine infusion to prevent a decrease in pressure with captopril. Reduction in sodium intake had no significant effect on arterial pressure, heart rate, or plasma volume, although arterial plasma angiotensin II concentration and renin activity were significantly increased (p less than 0.01). Infusion of angiotensin II produced a significant reduction in baroreceptor reflex sensitivity (p less than 0.01), and converting enzyme inhibition produced a significant increase (p less than 0.05). These effects accompanied significant increases and decreases in arterial angiotensin II concentration, respectively (p less than 0.01), but were independent of angiotensin II-related changes in arterial pressure. The data indicate that physiological variations in circulating angiotensin II have a direct effect on sensitivity of the baroreceptor-heart rate reflex.
Formation of angiotensin II by tonin-inhibitor complex.
Authors: Ikeda M , Sasaguri M , Maruta H , Arakawa K
Published: June 2012

Enzymatic activity of tonin-alpha 1-macroglobulin complex was studied in vitro and in vivo, using an immunoimmobilization technique. Tonin-alpha 1-macroglobulin complex, which was immunologically immobilized by anti-alpha 1-macroglobulin antibody covalently coupled to agarose gels, could quantitatively hydrolyze angiotensin I and synthetic tridecapeptide renin substrate to form angiotensin II. However, the solid-phase antibody-bound tonin-alpha 1-macroglobulin complex could not hydrolyze the plasma protein renin substrate. Phenylmethylsulfonyl fluoride, a serine protease inhibitor, inhibited both free tonin and the solid-phase antibody-bound tonin-alpha 1-macroglobulin complex. The hydrolytic activity of the solid-phase antibody-bound tonin-alpha 1-macroglobulin complex against angiotensin I was not inhibited by soybean trypsin inhibitor (molecular weight, 23,000), a potent inhibitor of free tonin. Taken together, these results suggest that tonin bound to alpha 1-macroglobulin keeps the active site intact and that inhibition of the enzyme activity is due to a steric hindrance. When 500 microliter of tonin was administered intravenously to rats, the immunoimmobilization method was used to show that the tonin-alpha 1-macroglobulin complex in the plasma formed angiotensin II. Thus, the tonin-alpha 1-macroglobulin complex in the plasma may be linked to some forms of hypertension through angiotensin II formation.
Cardiac hypertrophy in hypertension. Repolarization abnormalities elicited by rapid lowering of pressure.
Authors: Pepi M , Alimento M , Maltagliati A , Guazzi M D
Published: June 2012

In hypertension, coronary flow is augmented and oxygen balance is adequate despite an increase in coronary resistance. For the maintenance of flow in the presence of and after regression of ventricular hypertrophy, the ratio of pressure and ventricular mass must remain normal. Coronary reserve would be altered if treatment normalized pressure but not ventricular mass or if pressure were lowered too fast. We investigated 42 patients with primary hypertension. In 28 (Group I) left ventricular mass index (by ultrasound) was within the mean value +2 SD (96 + 38 g/m2) of 145 controls and exceeded these values in the remaining 14 patients (Group 2). The diastolic pressure was lowered rapidly to between 85 and 90 mm Hg with two potent vasodilators, nifedipine (sublingually) and nitroprusside, while a 12-lead electrocardiogram was recorded continuously. During both tests, seven patients in Group 2 (responders) showed inversion of normal T waves, in lead I, aVL, and V3-6. These changes waxed and waned in parallel with the pressure fall and recovery and were not attributable to alterations in adrenergic tone, conduction disturbances, variations, or group differences in the QRS axis, QTc interval, heart rate, left ventricular fractional shortening, wall stress, rate of dimension increase in early diastole, or isovolumic relaxation. A "steal phenomenon'' or passive collapse in compliant coronary lesions during vasodilatation seems unlikely; in fact, patients were free from coronary symptoms, and the electrocardiographic alterations occurred only in seven patients in Group 2, who had a greater left ventricular mass index and required a larger pressure drop to return the diastolic pressure to normal.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of a low fat diet on carbohydrate metabolism in patients with hypertension.
Authors: Parillo M , Coulston A , Hollenbeck C , Reaven G
Published: June 2012

Plasma glucose and insulin responses to both a 75-g oral glucose challenge and to conventional meals were determined in eight patients with hypertension and compared with values of a control population. The results indicated that patients with hypertension had significantly higher than normal plasma glucose and insulin concentrations in both situations. Furthermore, when dietary carbohydrate was increased by 16% of total calories (with a reciprocal reduction in dietary fat), the hyperglycemia and hyperinsulinemia present in patients with hypertension were accentuated. Since low fat-high carbohydrate diets are usually recommended for patients with hypertension, these data suggest that abnormalities of glucose and insulin metabolism associated with hypertension would be increased if patients with high blood pressure followed conventional dietary advice. Since hyperglycemia and hyperinsulinemia have been shown to be associated with an increased risk of developing coronary artery disease, it may be appropriate to reevaluate the clinical utility of low fat-high carbohydrate diets in the treatment of hypertension.
Race and sex differences in the correlates of blood pressure change.
Authors: Daniels S R , Heiss G , Davis C E , Hames C G , Tyroler H A
Published: June 2012

Potential predictors of systolic and diastolic blood pressure change between 1960 and 1967 in the biracial population of Evans County, Georgia, were investigated. An all possible regressions multiple linear regression analysis was used. For systolic blood pressure change, the level of systolic blood pressure, age, and change in Quetelet index were significant (p less than 0.05) correlates in white men. The level of systolic blood pressure, the level and change of socioeconomic status, change in Quetelet index, and change in cholesterol were significant correlates for white women. The level of Quetelet index was of borderline significance (p less than 0.055) when the other significant variables were included in the model for white women. The change in Quetelet index was the only significant correlate of systolic blood pressure change in blacks. For diastolic blood pressure change, age, change in hematocrit, and change in Quetelet index were significant correlates for white men. Age, level and change of socioeconomic status, level and change of Quetelet index, and change in hematocrit were the significant correlates in white women. In black men, change in Quetelet index and age were significant. In black women, only age was a significant correlate of diastolic blood pressure change. These results indicate that there may be important differences in these correlates between race-sex groups and thus in the mechanism of blood pressure change for different race-sex groups. groups.