bluuebunny/crossref_metadata_2025 huggingface dataset:
Renal Immunocytochemical Distribution and Pharmacological Properties of the Dual Angiotensin II/AVP Receptor
Authors: Gonzalez Carlos B. , Herrera Victoria L. M. , Ruiz-Opazo Nelson
Published: June 2012

Abstract
We have recently characterized a novel angiotensin II/vasopressin (Ang II/AVP) dual receptor coupled to adenylate cyclase and responding with equal sensitivity to Ang II and AVP. To gain insight into putative renal physiological roles of the dual Ang II/AVP receptor, we determined its pharmacological binding properties and renal immunocytochemical distribution. The effective displacement of [
3
H]AVP by [1-deamino-Val
14
,
d
-Arg
8
]-vasopressin (DVDAVP), a specific antidiuretic AVP analogue, supports a V
2
-type AVP receptor characteristic of the Ang II/AVP receptor. Displacement of
125
I–Ang II by losartan but not by PD 123319 defines the Ang II/AVP receptor as a novel AT
1
receptor isoform coupled to adenylate cyclase, in contrast to prototype Ca
2+
-mobilizing AT
1
receptors. Neither Ang II nor AVP displace each other, corroborating the predicted discrete binding domains for Ang II and AVP but presenting an enigma for the dissection of putative Ang II–and AVP-specific hierarchical roles of the dual Ang II/AVP receptor. The renal cytolocalization of the Ang II/AVP receptor to the outer medullary thick ascending limb tubules and inner medullary collecting ducts is consistent with the well-established AVP stimulation of sodium and water reabsorption in these tubules. These data suggest that the Ang II/AVP receptor might provide the molecular basis for the observed similar stimulatory effects of Ang II and AVP on renal tubular sodium and fluid reabsorption at physiological hormone concentrations.
Mechanical Stress of the Carotid Artery at the Early Phase of Spontaneous Hypertension in Rats
Authors: Cunha Roberto S. , Dabiré Hubert , Bezie Ivonic , Weiss Anne Marie , Chaouche-Teyara Kamel , Laurent Stéphane , Safar Michel E. , Lacolley Patrick
Published: June 2012

Abstract
Common carotid artery (CCA) hypertrophy has long been recognized in the neonatal period of development in spontaneously hypertensive rats (SHR), but the mean circumferential and shear stresses acting on the arterial wall have never been investigated in vivo. We investigated intra-arterial blood pressure in conscious rats, CCA diameter (echotracking techniques), blood flow velocity (pulsed Doppler), wall thickness (histomorphometry), and ganglionic blockade (hexamethonium) in Wistar rats and SHR at 5 and 12 weeks of age. During this interval, weight gain was identical in the strains, whereas the increase in wall thickness and blood pressure was greater in SHR. CCA diameter was identical at week 5 and increased similarly at week 12 in both strains. During ganglionic blockade, a larger diameter was observed in SHR at week 5 for the same BP level, whereas equivalent values were observed at week 12. Blood flow velocity decreased with age but to a significantly greater extent in SHR. Mean circumferential stress and shear stress index were identical in both strains at week 12. However, from weeks 5 to 12, mean circumferential stress increased with age similarly in both strains, whereas the age-related decrease in mean shear stress index was much greater in SHR than Wistar rats. Thus, despite a higher blood pressure, SHR exhibit the same carotid diameter as Wistar rats during early development. Because the kinetics of shear stress are different in both strains, altered flow-dilatation mechanisms, and possibly resulting endothelial dysfunction, may be involved in the diameter changes.
Reduced Dietary Potassium Reversibly Enhances Vasopressor Response to Stress in African Americans
Authors: Sudhir Krishnankutty , Forman Alex , Yi Sai-Li , Sorof Jonathan , Schmidlin Olga , Sebastian Anthony , Morris R. Curtis
Published: June 2012

Abstract
Acute vasopressor responses to stress are adrenergically mediated and hence potentially subject to differential modulation by dietary potassium and sodium. The greater vasopressor responsiveness in blacks compared with whites might then be consequent not only to a high dietary salt intake but also to a marginally reduced dietary potassium intake. Under controlled metabolic conditions, we compared acute vasopressor responses to cold and mental stress in black and white normotensive men during three successive dietary periods: (1) while dietary potassium was reduced (30 mmol K
+
/70 kg per day) and salt was restricted (10 to 14 days); (2) while salt was loaded (15 to 250 mmol Na
+
/70 kg per day) (7 days); and (3) while salt loading was continued and potassium was either supplemented (70 mmol K
+
/70 kg per day) (7 to 21 days) in 9 blacks and 6 whites or continued reduced (30 mmol K
+
/70 kg per day) (28 days) in 4 blacks (time controls). At the lower potassium intake, cold-induced increase in forearm vascular resistance in blacks was twice that in whites during both salt restriction and salt loading. Normalization of dietary potassium attenuated cold-induced increases in both forearm vascular resistance and systolic and diastolic blood pressures in blacks but only in systolic pressure in whites. In blacks but not in whites, normalization of dietary potassium attenuated mental stress–induced increases in systolic and diastolic pressures. In normotensive blacks but not whites, a marginally reduced dietary intake of potassium reversibly enhances adrenergically mediated vasopressor responsiveness to stress. That responsiveness so enhanced over time might contribute to the pathogenesis of hypertension in blacks.
Baroreflex Control of Heart Rate and Cardiac Hypertrophy in Angiotensin II–Induced Hypertension in Rabbits
Authors: Malpas Simon C. , Groom Andrew S. , Head Geoffrey A.
Published: June 2012

Abstract
The cardiac hypertrophy observed in hypertension is thought to be responsible for the accompanying deficiency in the baroreflex control of heart rate. In this study, we assessed the baroreflex relationship between heart rate and arterial pressure in a group of seven rabbits during a normotensive period, during the early phase of angiotensin II (Ang II)–induced hypertension (1 week) (50 ng/kg per minute IV via osmotic minipumps), after 7 weeks of continuous hypertension, then 2 days after Ang II was stopped, and finally 7 days after Ang II. Left ventricles were weighed for measurement of left ventricular weight–body weight ratio. One week of intravenous Ang II infusion produced hypertension (mean arterial pressure from 80±2 up to 115±8 mm Hg), with significantly increased heart rate and hematocrit. The heart rate–arterial pressure baroreflex curve was shifted to the right, with a significant 45% reduction in the gain of the reflex (−6.4±1.5 to −3.5±0.2 beats per minute/mm Hg). After 7 weeks of Ang II, arterial pressure was still elevated (112±4 mm Hg) and the gain of the baroreflex curve still somewhat attenuated, although it was no longer markedly different from normotensive levels (gain, −5.09±0.95, 20% reduction from normotensive level). Two days after the Ang II infusion was stopped, arterial pressure had returned to normotensive levels, although hematocrit and heart rate remained elevated. At this time, the baroreflex curve was similar to prehypertensive control levels, with no further changes when measured again 7 days after Ang II. Cardiac hypertrophy was present when measured at 7 days after angiotensin (left ventricular weight–body weight ratio: 1.78±0.05 versus 1.35±0.04 g/kg, hypertensive versus normotensive,
P
<.05). Thus, although Ang II infusion produced an initial deficit in the baroreflex control of heart rate, this effect became less as the hypertension continued. Furthermore, although cardiac hypertrophy developed, its presence did not appear to be sufficient to produce a decrease in barosensitivity independent of raised arterial pressure.
Cyclosporine Impairs the Ability of Human Platelets to Mediate Vasodilation
Authors: Óskarsson Helgi J. , Hofmeyer Timothy G. , Olivari Maria Theresa
Published: June 2012

Abstract
Cyclosporine causes various platelet abnormalities. Whether it affects the ability of platelets to mediate vasodilation is unknown. Platelets were isolated from healthy volunteers and 13 heart transplant patients on cyclosporine. When perfused through preconstricted normal rabbit carotid arteries, activated platelets from transplant patients failed to cause vasorelaxation, whereas normal platelets produced significant vasodilation (−4.0±1.9% versus 30±3% [
P
<.0001] change in vessel diameter, respectively). When normal platelets were exposed to cyclosporine in vitro, they lost their ability to cause vasodilation in a dose- and time-dependent fashion. However, when activated and perfused through quiescent,
N
ω
-nitro-
l
-arginine–pretreated arteries, platelets from transplant patients and normal platelets caused similar degrees of vasoconstriction. The amount of adenosine triphosphate in the supernatant from activated cyclosporine-exposed and control platelets was similar (1.7±0.4 versus 1.5±0.3 μmol/L [
P
=NS], respectively). However, concomitant perfusion of activated platelets from transplant patients impaired acetylcholine-mediated, endothelium-dependent vasodilation but perfusion of normal platelets did not. Although cyclosporine-exposed platelets showed an impaired ability to produce vasorelaxation, supernatant from the same platelets caused near normal vasodilation. Human platelets exposed to cyclosporine have an impaired ability to mediate vasodilation. This is not due to increased platelet-mediated vasoconstriction or a decrease in the release of platelet-derived nucleotides but rather to a short-acting compound released by cyclosporine-exposed platelets that interferes with endothelium-dependent vasodilation.
Urinary kallikrein activity and renal vascular resistance in the antihypertensive response to thiazide diuretics.
Authors: O'Connor D T , Preston R A , Mitas J A , Frigon R P , Stone R A
Published: June 2012

To evaluate the mechanism of chronic thiazide diuretic action in hypertension, we treated 19 essential hypertensive white men for 1-month periods on placebo alone and hydrochlorothiazide alone. During therapy, mean arterial pressure (MAP) fell, but radioisotopically determined intravascular volume remained unchanged, suggesting other mechanisms of thiazide action upon blood pressure. In the renal circulation, thiazides did not change renal plasma flow or glomerular filtration rate, but renovascular resistance was diminished, probably at the afferent arteriole. Concomitant with the decline in blood pressure and renovascular resistance, urinary kallikrein excretion increased, from subnormal (hypertensive) levels back into the normal range. The kallikrein increase did not correlate with changes in plasma aldosterone. In addition, patients with blood pressure responses (reduction greater than or equal to 10%) to thiazides (n = 12) had greater increases in kallikrein excretion than those without such a blood pressure decrement (n = 7), suggesting a role for renal kallikrein in the hypotensive response to thiazide diuretics.
Role of kinins in the acute antihypertensive effect of the converting enzyme inhibitor, captopril.
Authors: Carretero O A , Miyazaki S , Scicli A G
Published: June 2012

The role of kinins in the acute antihypertensive effect of a converting enzyme inhibitor (CEI) was studied in sodium-depleted normotensive and in two-kidney, one clip chronically hypertensive rats (2K-1C). The 2K-1C were on a normal sodium diet. The acute vasodepressor effect of the CEI was determined in these two groups either after administration of normal rabbit globulins or antikinin globulins. The amount of kinin antibodies administered completely blocked the hypotensive effects of bradykinin, 400 ng/kg, and urinary kallikrein, 4 microgram/kg. After administration of CEI in the sodium-depleted rats there was no significant difference (p greater than 0.05) in the acute changes in mean blood pressure (BP) between the group pretreated with normal rabbit globulins (delta BP -32.3 +/- 3.9 mm Hg) and the group pretreated with antikinin globulins (delta BP -25 +/- 2.5 mm Hg). In the 2K-1C pretreated with normal rabbit globulins, the CEI produced a decrease in BP of -21 +/- 4.5 mm Hg. This decrease was almost completely blocked in the group pretreated with the antikinin globulins (delta BP -4 +/- 4.1 mm Hg). These differences in the changes in BP were significant (p less than 0.02). These results suggest that the acute antihypertensive effect of the CEI in the sodium-depleted rats is probably due to inhibition of the conversion of angiotensin I to II while in the 2K-1C it is due, in part, to an increase in kinin concentrations secondary to the inhibition of kininase II.
Renal artery stenosis with normal angiotensin II values. Relationship between angiotensin II and body sodium and potassium on correction of hypertension by captopril and subsequent surgery.
Authors: Atkinson A B , Brown J J , Davies D L , Leckie B , Lever A F , Morton J J , Robertson J I
Published: June 2012

The case is reported of a young woman with severe hypertension, unilateral renal artery stenosis, variously normal or marginally high plasma concentrations of active renin, angiotensin II, aldosterone, sodium, and potassium; and normal total exchangeable and total body sodium and potassium. Arteriograms and ureter catheterization showed the stenosis to be severe, but the unstimulated renal vein renin and angiotensin II differential to be modest. Captopril caused an initial fall in angiotensin II and arterial pressure. During prolonged captopril treatment, plasma angiotensin II and aldosterone remained depressed; exchangeable and total body sodium and potassium were unaltered. Blood pressure fell further to normal levels during prolonged captopril treatment, while subsequent surgical correction of the renal artery stenosis was curative; absolute values of blood pressure and plasma angiotensin II were similar in both situations. The findings support, without proving, the concept that chronic modest elevation of angiotensin II may be responsible for sustained hypertension in unilateral renal artery stenosis. Patients of this type contrast sharply with those, also with severe renal artery stenosis or occlusion, who have gross elevation of renin, angiotensin II, and aldosterone, with sodium and potassium deficiency. Captopril or surgery are effective in both syndromes, but the manner of response to treatment differs markedly.
Purification of tonin by affinity chromatography.
Authors: Ikeda M , Gutkowska J , Thibault G , Boucher R , Genest J
Published: June 2012

Tonin has been purified from rat submaxillary glands. The purification procedure included affinity chromatography on Sepharose 4B coupled to antitonin followed by DEAE chromatography and gel filtration on Sephadex G-100. Homogeneity of the purified enzyme was confirmed by Sephadex G-100 gel filtration, disc electrophoresis, and isoelectric focusing on polyacrylamide gel, immunodiffusion, and immunoelectrophoresis. The tonin was purified 11.5-fold, with 35% recovery. The purified tonin has full enzymatic or immunological activity.
Responses of juxtaglomerular cell suspensions to various stimuli.
Authors: Khayat A , Gonda S , Sen S , Smeby R R
Published: June 2012

Cell suspensions were prepared from rat renal cortical tissue by dispersion with 0.1% collagenase. Unit gravity sedimentation in a 1%-4% Ficoll gradient resulted in a single-cell suspension enriched in juxtaglomerular (JG) cells. Both the cellular renin activity and the amount of renin released into the supernatant increased with time when the suspensions were incubated for 1 hour at 37 degrees C in tissue culture medium. These cells responded to epinephrine and norepinephrine by increasing both synthesis and release of renin. The response was blocked by timolol but not by phenoxybenzamine. Cell suspensions prepared in the same manner but using 0.25% trypsin as the dispersing enzyme neither synthesized nor released renin into the tissue culture medium when similarly incubated. Trypsin-dispersed cells did not respond to catecholamine stimulation. Renin synthesis and release in collagenase-dispersed JG cells were unaltered by changes in Na, K, or Ca ion concentrations. Angiotensin II inhibited release, while saline extracts of clipped kidney from renal hypertensive rats stimulated renin release by these cells.
Prolonged isometric exercise. Part 1: Effect on circulation and on renal excretion of sodium and potassium in mild essential hypertension.
Authors: Parfrey P S , Wright P , Ledingham J M
Published: June 2012

The effect of stress, in the form of prolonged isometric exercise, on the circulation and on the renal excretion of sodium and potassium was studied in 18 patients with mild essential hypertension. Thirteen men and five women, aged 20 to 50 years with basal diastolic blood pressure (BP) between 90 and 110 mm Hg were matched by age, sex, and race with 18 controls who had basal diastolic BPs less than 85 mm Hg. After the subjects rested for 90 minutes, basal measurements of pulse rate, BP, and rates of sodium and potassium excretion were made. The subjects then underwent a 1-hour period of isometric exercise involving all four limbs in rotation, followed by 5 hours of rest during which the measurements were repeated at half-hourly intervals for the first 2 hours and at hourly intervals for the last 3 hours. On another day, the subjects were again studied after 1 hour of resting instead of exercise. Responses of each subject were then expressed as ratios of changes from the basal values observed on the exercise and rest days. Changes in systolic and diastolic BP and hart rate were not significantly different in the hypertensive and control groups. In hypertensive subjects, the rate of sodium and potassium excretion was decreased after isometric exercise compared with the rest day, whereas in normal subjects this response was reversed. For the first 3 hours after exercise, the cation excretion rate of the hypertensive group was significantly less than that of the control group. These results indicate that isometric exercise in mild hypertension induces prolonged renal retention of both sodium and potassium.
Cost-effectiveness of a worksite hypertension treatment program.
Authors: Logan A G , Milne B J , Achber C , Campbell W P , Haynes R B
Published: June 2012

The cost-effectiveness of treating hypertension at the patient's place of work was compared in a randomized controlled trial with care delivered in a community. The average total cost per patient for worksite care in this 12-month study was not significantly different from that for regular care ($242.86 +/- 6.94 vs $211.34 +/- 18.66, mean +/- SEM). The worksite health system cost was significantly more expensive ($197.36 +/- 4.99 vs $129.33 +/- 13.34, p less than 0.001) but the patient cost was significantly less ($45.40 +/- 3.23 vs $82.00 +/- 6.20, p less than 0.01). The mean reduction in diastolic blood pressure (BP) at the year-end assessment was significantly greater in the worksite group (12.1 +/- 0.6 vs 6.5 +/- 0.6 mm Hg, p less than 0.001). The incremental cost-effectiveness ratio of $5.63 per mm Hg for worksite care was less than the base cost-effectiveness ratio of $32.51 per mm Hg for regular care, indicating that the worksite program was substantially more cost-effective. Our findings support health policies that favor allocating resources to work-based hypertension treatment programs for the target group identified in this study.
Central opiate system modulation of the area postrema pressor pathway.
Authors: Szilagyi J E , Ferrario C M
Published: June 2012

Angiotensin II, when given into the vertebral arteries, acts at the area postrema to augment central sympathetic vasomotor activity. The mechanism of action is unknown but recent evidence implicates an interaction with the opiate system. In dogs anesthetized with chloralose either alone or in combination with morphine, naloxone blunted the pressor response to vertebrally administered angiotensin II by 50%. Addition of morphine to dogs anesthetized with chloralose only doubled the pressor response to identical doses of angiotensin II. On the other hand, the magnitude of the pressor responses to intravenously infused angiotensin II were unaltered by either naloxone or morphine. Likewise, responses to norepinephrine given vertebrally and intravenously were not similarly affected. Therefore, naloxone-induced changes in vascular responsiveness were not responsible for the altered sensitivity of the area postrema to angiotensin II following blockade of endogenous opiates. The data suggest that there exists a previously unrecognized interaction of the endogenous opiate system in the medulla in mediating the pressor effects of angiotensin II at the level of the area postrema.
Role of the renal nerves in the pathogenesis of one-kidney renal hypertension in the rat.
Authors: Katholi R E , Winternitz S R , Oparil S
Published: June 2012

Increased sympathetic nervous system activity has been demonstrated in established one-kidney one clip hypertension in the rat. To determine the importance of the renal nerves in this model of hypertension, renal denervation or sham operation was carried out 2 weeks after clipping. Systolic blood pressure (BP) after clipping the renal artery in 27 uninephrectomized male Charles River rats increased significantly from 125 +/- 3 mm Hg to a stable level of 185 +/-7 mm Hg by 2 weeks, in association with a positive sodium balance. Renal denervation in 13 animals resulted in a significant decrease in BP to 137 +/- 7 mm Hg, while no change in BP was seen after sham operation in 14 animals. There was no difference in mean daily water intake, mean daily sodium intake, mean daily urine volume, or mean fractional urinary sodium excretion between sham-operation and renal-denervated animals during the 2 weeks after operation. Plasma renin activity (PRA) and creatinine clearance were not significantly different at sacrifice 2 weeks after operation. Six of the renal-denervated rats were followed for 11 weeks after surgery. The BP rose again to hypertensive levels (187 +/- 8 mm Hg) by 5 weeks after renal denervation. Repeat renal denervation resulted in a significant decrease to 142 +/- 8 mm Hg. Renal denervation in eight rats with established one-kidney Grollman hypertension (185 +/- 8 mm Hg) also resulted ina significant decrease in systolic BP (143 +/- 8 mm Hg). The data demonstrate the importance of intact renal nerves in the maintenance of hypertension in the one-kidney renal hypertensive rat. The depressor effect of renal denervation is not mediated by alterations in sodium intake or excretion, water intake or excretion, creatinine clearance or PRA.
Is vasopressin an important hypertensive hormone?
Authors: Lohmeier T E , Smith M J , Cowley A W , Manning R D , Guyton A C
Published: June 2012

To generate quantitative data relating to the potential hypertensive activity of arginine vasopressin (AVP), 140 and 560 microunits AVP/kg/min were infused chronically in both normotensive dogs and dogs made hypertensive by chronic infusion of either angiotensin II (AII) or aldosterone. The lower rate of AVP infusion increased plasma AVP concentration from 0.4 +/- 0.1 microunits/ml. Mean arterial pressure (MAP) was recorded 24 hours per day, and all dogs were infused continuously with 800 ml of isotonic saline per day. During the initial days of AVP infusion in normotensive dogs, natriuresis, kaliuresis, and water retention were prominent and MAP increased progressively to a peak on Day 6 (30 mm Hg above control). Subsequently, diuresis ensued, net water retention decreased, and MAP fell progressively to only 13 mm Hg above control by Day 12 of AVP infusion. In contrast, in AII or aldosterone hypertensive dogs during AVP infusion, the natriuresis was greatly attenuated, water balance was unchanged or even negative, and MAP either did not increase or increased only transiently. When AVP infusion was terminated in dogs given only AVP, diuresis occurred, and MAP fell gradually over a period of hours to hypertensive levels. In marked contrast, cessation of AVP infusion in dogs with either AII or aldosterone hypertension was associated with a precipitous fall in MAP of 35 to 40 mm Hg within 1 hour: however, this reduction was only transient - over the subsequent hours, both salt and water retention occurred, and MAP returned to previous hypertensive levels. Thus, in the hypertensive models studied, high plasma levels of AVP had relatively weak hypertensive effects. Although variations in plasma AVP concentration were associated with rather pronounced acute effects on MAP, the long-term changes in MAP produced by AVP were either minimal or, in the case of the animals made hypertensive by other agents, nonexistent.
Pressor responses to centrally-administered prostaglandin E2 in spontaneously hypertensive rats.
Authors: Takahashi H , Buñag R D
Published: June 2012

Blood pressure (BP) and heart rate became elevated when prostaglandin E2, (PGE2) was infused into the cerebral ventricles of awake and anesthetized rats. Frequency of sympathetic neural firing was also increased. While the magnitude of the pressor responses was larger in spontaneously hypertensive rats (SHRs) than in normotensive ones (NTRs), the accompanying increases in sympathetic nerve firing were not significantly different. Pressor effects were appreciable within 2 minutes after the start of th PGE2 infusion did not become maximal until 15 minutes later. By contrast, acceleration in sympathetic nerve firing was maximal within 2 minutes and then dwindled or remained stationary thereafter. Removal of sympathetic vasomotor tone by cervical section of the spinal cord abolished early phases without affecting subsequent peaks of the pressor response. The overall height of the pressor responses in hypophysectomized NTRs was half that in sham-operated controls. These results suggest that GPE2 acts centrally to elevate BP by increasing not only the sympathetic discharge but perhaps also the secretion of hypophysial hormones, such a vasopressin. In light of previous studies showing that SHRs secrete mor vasopressin, it was considered possible that their enhanced pressor responsiveness to PGEs could result from a greater release o endogenous vasopressin.
Effects of stress on blood pressure and cardiac pathology in rats with borderline hypertension.
Authors: Lawler J E , Barker G F , Hubbard J W , Schaub R G
Published: June 2012

Repeated attempts to produce hypertension (HT) through psychological stress have failed to elevate blood pressure (BP) to levels seen in chronic, untreated essential HT in humans. In general, these studies have two characteristics in common: they utilize the normotensive animal, with no genetic history of HT, and they involve stressors to which animals readily adapt. The present study utilized offspring with one HT parent. The male F1, offspring of SHR x WKY had borderline HT (-/x +/- SEM = 152.4 +/- 1.34 mm Hg). With a conflict paradigm used as the stressor, experimental animals eventually developed severe HT (188.3 +/- 2.70 mm Hg) compared to two non-stressed control groups (158.4 +/- 2.31 mm Hg and 151.9 +/- 2.25 mm Hg). After 15 weeks of stress for 2 hours daily, termination of conflict for 10 weeks did not reduce the HT in experimental animals. Subsequent analyses revealed that stressed animals, when compared to nonstressed controls, exhibited elevated heart-weight-to-body-weight ratios and significant cardiac pathology in the form of myofibrillar degeneration, accumulation of inflammatory cells, and fibrosis. The implications of using this model for the analysis of cardiovascular concomitants of stress-induced HT are discussed.
Effects of bromocriptine on responses to stress in spontaneously hypertensive rats.
Authors: Sowers J R
Published: June 2012

Treatment of 2-month-old spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto (WKY) normotensive controls with the dopamine agonist, bromocriptine, for 7 days significantly affected hormonal responses to immobilization stress in both groups. However, basal blood pressures and pressor responses to immobilization stress were significantly reduced only in SHR. Basal levels of catecholamines were similar in the two groups of rats, but catecholamine responses to immobilization stress following saline (vehicle) treatment were marked greater in SHR; following bromocriptine treatment for 7 days, catecholamine responses were similar in the two groups. Basal serum prolactin levels and prolactin responses to immobilization were greater in SHR after saline treatment; after bromocriptine, they were similar in the two groups. Basal plasma renin activity (PRA)and PRA responses to immobilization were significantly less in SHR following saline treatment; after bromocriptine treatment these responses were paradoxically greater in SHR without being significantly changed in WKY. Basal levels of plasma aldosterone and corticosterone following saline were significantly greater, but responses to immobilization less, in SHR. Bromocriptine treatment decreased aldosterone and corticosterone responses to stress in WKY but paradoxically increased these responses in SHR. These results suggest that increased pressor responses to stress are dependent on heightened sympathetic nerve activity, perhaps secondary to decreased central dopaminergic activity. Increased basal prolactin levels and stress-mediated prolactin responses may be related to decreased central dopaminergic activity. Paradoxical PRA, plasma aldosterone, and corticosterone responses to stress following bromocriptine suggest altered dopaminergic modulation of these hormones in the SHR.
Plasma norepinephrine during stress in essential hypertension.
Authors: Goldstein D S
Published: June 2012

Comparative studies of plasma norepinephrine in patients with essential hypertension and in normotensive controls have consistently reported higher mean resting levels of norepinephrine in the hypertensive groups, but the hypertensive-normotensive differences have often been small and, in about three-fifths of the studies, not statistically significant. The author reviewed the medical literature to test the hypothesis that, during stress, hypertensive-normotensive differences in norepinephrine become more apparent. Among 24 studies involving orthostatic stress, the increment in norepinephrine with standing was similar for hypertensives and normotensives (239 vs 230 pg/ml). In contrast, among eight studies involving exercise, the increment in norepinephrine was significantly greater in hypertensives (834 vs 450 pg/ml). For both standing and isotonic exercise, absolute changes in norepinephrine with stress correlated with basal norepinephrine across the hypertensive but not the normotensive groups. These results are consistent with the existence within the hypertensive population of a subgroup of patients with elevated norepinephrine levels at rest and excessive sympathetic responsiveness to stress. However, the available literature is decidedly lacking in studies about other types of stress besides standing and exercise.
Portable blood pressure measurements: performance of Korotkov sound analysis techniques.
Authors: Wolthuis R , Hull D , MacAfoose D , Fischer J
Published: June 2012

Noninvasive portable blood pressure systems (PBPS) are typically based on korotkov sound technique. The performance of related Korotkov sound analysis techniques was assessed in PBPS data obtained from nine normotensive and nine hypertensive men. Multiple-seated PBPS measurements were taken, each following 1 minute of quiet rest, moderate walking, and stair climbing; each PBPS measurement was accompanied by a simultaneous auscultatory measurement in the same arm. In subsequent manual PBPS data analysis, PBPS systolic and diastolic BPs were within 4 mm Hg of corresponding auscultatory BPs 86% and 88% of the time; BPs following rest and walking showed greater accuracy, while those following stair climbing were less accurate. Interestingly, automated analysis of diastolic PBPS data (using selective bandpass filtering, amplitude normalization, and comparator decision ratios) provided a level of accuracy similar to that obtained from manual data analysis. Overall, both manual and automated Korotkov sound analysis techniques can provide BP results that agree quite well with auscultatory determinations.
Induction of Mitogen-Activated Protein Kinase Phosphatase-1 During Acute Hypertension
Authors: Xu Qingbo , Fawcett Timothy W. , Gorospe Myriam , Guyton Kathryn Z. , Liu Yusen , Holbrook Nikki J.
Published: June 2012

Abstract
Recently, we demonstrated that elevated blood pressure activates mitogen-activated protein (MAP) kinases in rat aorta. Here we provide evidence that the vascular response to acute hypertension also includes induction of MAP kinase phosphatase-1 (MKP-1), which has been shown to function in the dephosphorylation and inactivation of MAP kinases. Restraint or immobilization stress, which leads to a rapid rise in blood pressure, resulted in a rapid and transient induction of
MKP-1
mRNA followed by elevated MKP-1 protein expression in rat aorta. That the induction of MKP-1 by restraint was due to the rise in blood pressure was supported by the finding that several different hypertensive agents (phenylephrine, vasopressin, and angiotensin II) were likewise capable of eliciting the response, and sodium nitroprusside, a nonspecific vasodilator agent that prevented the acute rise in blood pressure in response to the hypertensive agents, abrogated
MKP-1
mRNA induction. The in vivo effects could not be mimicked by treatment of cultured aortic smooth muscle cells with similar doses of the hypertensive agents. These findings support a role for MKP-1 in the in vivo regulation of MAP kinase activity during hemodynamic stress.
Erythrocyte Sodium-Lithium Countertransport in Non-Modulating Offspring and Essential Hypertensive Individuals
Authors: Sánchez Ramiro A. , Giménez María I. , Migliorini Mercedes , Giannone Carlos , Ramírez Agustín J. , Weder Alan B.
Published: June 2012

Abstract
Non-modulators are a subset of essential hypertensive individuals in whom renal hemodynamic and adrenal aldosterone responses to angiotensin II fail to modulate appropriately during high dietary salt intake. The main aim of this study was to investigate the familial aggregation of non-modulation and several erythrocyte Na
+
transport systems in normotensive and hypertensive individuals as well as offspring of hypertensive parents. An additional aim was to evaluate the effect of treatment with enalapril on erythrocyte Na
+
transport. We studied 15 normotensive subjects (6 males, 27±6 years), 14 untreated modulating essential hypertensive subjects (7 males, 38±7 years), 12 untreated non-modulating essential hypertensive subjects (7 males, 38±6 years), 14 modulating offspring of hypertensive parents (8 males, 25±6 years), and 14 non-modulating offspring of hypertensive parents (8 males, 26±4 years). Blood pressure was recorded with an oscillometric device and renal plasma flow and glomerular filtration rate by clearances of para-aminohippurate and inulin, respectively. Non-modulating subjects were identified as individuals who failed to increase effective renal plasma flow by 30% and decrease filtration fraction by at least 30% 10 days after changing from a low (20 mmol/d) to a high (250 mmol/d) sodium intake. Erythrocyte Na
+
transport was characterized by measurements of the Na
+
-K
+
pump, Na
+
-Li
+
countertransport, Na
+
-K
+
-Cl
−
cotransport, passive Na
+
permeability, and Na
+
content. After the initial studies, hypertensive individuals were treated with enalapril (20 mg/d PO) for 6 months, after which erythrocyte Na
+
transport measurements were again made. The main findings were that Na
+
-Li
+
countertransport is increased in non-modulating hypertensive subjects and non-modulating offspring of hypertensive parents, that the increase in blood pressure in response to high salt intake is greater in non-modulating than modulating hypertensive subjects, and that enalapril decreases Na
+
-Li
+
countertransport activity to normal in non-modulating hypertensive subjects. These findings provide support for a possible genetic role in the development of salt sensitivity and suggest that Na
+
-Li
+
countertransport and non-modulation are related phenotypes.
Angiotensin-(1-7) Induces Bradykinin-Mediated Hypotensive Responses in Anesthetized Rats
Authors: Abbas Asad , Gorelik G. , Carbini L. A. , Scicli A. G.
Published: June 2012

Abstract
Angiotensin-(1-7) [Ang-(1-7)] reportedly potentiates hypotensive responses to bradykinin. We studied whether increases in circulating bradykinin would alter responses to Ang-(1-7). In rats anesthetized with thiobutabarbital, bradykinin infusion (5 μg/kg per minute IA) resulted in a rapid decrease in mean arterial pressure (MAP) of about 20 mm Hg (
P
<.01, n=9), although MAP slowly increased by 10 mm Hg after 15 minutes. When Ang-(1-7) (20, 80, and 380 nmol per rat IA) was given during bradykinin infusion, it elicited hypotension at 80 and 380 nmol (ΔMAP: −15±2.7 and −21±3.3 mm Hg, respectively;
P
<.001); this hypotension was not affected by the angiotensin type 1 antagonist L-158,809 (200 μg/kg IA), the angiotensin type 2 antagonist PD 123319 (10 mg/kg IA), saralasin, or sarthran (10 μg/kg per minute). The bradykinin type 2 receptor antagonist icatibant (30 μg per rat) eliminated the hypotensive responses to Ang-(1-7), which now increased MAP at all doses tested (
P
<.005). Thus in the presence of bradykinin, Ang-(1-7) induces hypotensive responses that are blocked by icatibant and unaffected by angiotensin receptor antagonists. Ang-(1-7) given to saline-infused rats elicited hypertensive responses at all doses (ΔMAP: 6.4±1.5, 12±1.6, and 16.3±2.7 mm Hg, respectively;
P
<.01); these responses were abolished by L-158,809 and sarthran. In rats pretreated with saralasin, Ang-(1-7) induced hypotension at 80 and 380 nmol (ΔMAP: −7.7±2.3 and −9.5±2.7, respectively;
P
<.05), whereas icatibant abolished this response. Thus in the rat, Ang-(1-7) can decrease blood pressure by a mechanism involving the bradykinin type 2 receptor and participates with bradykinin in a vasodepressor pathway that may serve a counterregulatory role, modulating the vasoconstrictor effects of Ang II.
Effect of Bilateral Nephrectomy on Active Renin, Angiotensinogen, and Renin Glycoforms in Plasma and Myocardium
Authors: Katz Stephen A. , Opsahl John A. , Lunzer Mary M. , Forbis Lynn M. , Hirsch Alan T.
Published: June 2012

Abstract
In an attempt to clarify the relationship of the circulating and myocardial renin-angiotensin systems, active renin concentration, its constituent major glycoforms (active renin glycoforms I through V), and angiotensinogen were measured in plasma and left ventricular homogenates from sodium-depleted rats under control conditions or 2 minutes, 3 hours, 6 hours, and 48 hours after bilateral nephrectomy (BNX). Control myocardial renin concentration was 1.4±0.1 ng angiotensin I (Ang I) per gram myocardium per hour and plasma renin concentration was 6.7±1.1 ng Ang I per milliliter plasma per hour. Control myocardial angiotensinogen was 0.042±0.004 μmol/kg myocardium and plasma angiotensinogen was 1.5 μmol/L plasma. Two minutes after BNX and corresponding stimulation of renin secretion by anesthesia and surgery, plasma renin concentration was increased disproportionately compared with myocardial renin. Three, 6, and 48 hours after BNX, renin decay occurred significantly faster from the plasma than from the myocardium. Forty-eight hours after BNX, myocardial renin concentrations had fallen to 15% of control values, while myocardial angiotensinogen concentrations had increased 12-fold and plasma angiotensinogen concentrations had increased by only 3.5-fold. Myocardial renin glycoform proportions were identical in myocardial homogenates and plasma in control animals. At 6 hours BNX, the proportions of plasma active renin glycoforms I+II fell, while those in the myocardium significantly increased. We conclude that in control rats, active renin and active renin glycoforms are distributed as if in diffusion equilibrium between plasma and the myocardial interstitial space. After BNX, myocardial renin concentration falls dramatically, suggesting that most cardiac renin is derived from plasma renin of renal origin. After BNX, renin glycoforms I+II are preferentially cleared from the plasma but preferentially retained by the myocardium. Control myocardial angiotensinogen concentrations are too low to result from simple diffusion equilibrium between plasma and the myocardial interstitium.
Effects of Blood Pressure Control on Progressive Renal Disease in Blacks and Whites
Authors: Hebert Lee A. , Kusek John W. , Greene Tom , Agodoa Lawrence Y. , Jones Camille A. , Levey Andrew S. , Breyer Julia A. , Faubert Pierre , Rolin Henry A. , Wang Shin-Ru
Published: June 2012

Abstract
African Americans (blacks) have a disproportionately high incidence of end-stage renal disease due to hypertension. The Modification of Diet in Renal Disease (MDRD) Study found that strict blood pressure control slowed the decline in glomerular filtration rate (GFR) only in the subgroup of patients with proteinuria. The present report compares the effects of blood pressure control in black and white MDRD Study participants. Fifty-three black and 495 white participants with baseline GFRs of 25 to 55 mL/min/1.73 m
2
were randomly assigned to a usual or low mean arterial pressure (MAP) goal of ≤107 or ≤92 mm Hg, respectively. GFR decline was compared between randomized groups and correlated with the level of achieved blood pressure. The mean (±SE) GFR decline over 3 years in the low blood pressure group was 11.8±7.3 mL/min slower than in the usual blood pressure group among blacks (
P
=.11) compared with 0.3±1.3 mL/min slower among whites (
P
=.81) (
P
=.12 between blacks and whites). In both blacks and whites, higher baseline urine protein excretion was associated with a greater beneficial effect of the low MAP goal on GFR decline (
P
=.02 for both races). Combining both blood pressure groups and controlling for baseline characteristics, higher follow-up achieved MAP was associated with faster GFR decline in both blacks (
P
<.001) and whites (
P
=.002), with a sevenfold stronger relationship in blacks (
P
<.001). These secondary analyses support the prior recommendation for a lower than usual blood pressure goal (MAP ≤92 mm Hg) in black and white patients with proteinuria (>1 g/d). In addition, a lower level of blood pressure control may be even more important in blacks than in whites in slowing the progression of renal disease.
Counterregulatory Actions of Angiotensin-(1-7)
Authors: Ferrario Carlos M. , Chappell Mark C. , Tallant E. Ann , Brosnihan K. Bridget , Diz Debra I.
Published: June 2012

Abstract
Angiotensin (Ang)-(1-7) is a bioactive component of the renin-angiotensin system that is formed endogenously from either Ang I or Ang II. The first actions described for Ang-(1-7) indicated that the peptide mimicked some of the effects of Ang II, including the release of prostanoids and vasopressin. However, Ang-(1-7) is devoid of vasoconstrictor, central pressor, or thirst-stimulating actions. In fact, new findings reveal depressor, vasodilator, and antihypertensive actions that may be more apparent in hypertensive animals or humans. Thus, the accumulating evidence suggests that Ang-(1-7) may oppose the actions of Ang II either directly or by stimulation of prostaglandins and nitric oxide. These observations are significant because they may explain the effective antihypertensive action of converting enzyme inhibitors in a variety of non–renin-dependent models of experimental and genetic hypertension as well as most forms of human hypertension. In this context, studies in humans and animals showed that the antihypertensive action of converting enzyme inhibitors correlated with increases in plasma levels of Ang-(1-7). In this review, we summarize our knowledge of the mechanisms accounting for the counterregulatory actions of Ang-(1-7) and elaborate on the emerging concept that Ang-(1-7) functions as an antihypertensive peptide within the cascade of the renin-angiotensin system.
Comparative Effect of PGE
2
and PGI
2
on Renal Function
Authors: Villa Eduardo , Garcia-Robles Rafael , Haas John , Romero Juan Carlos
Published: June 2012

Abstract
Rapid degradation of prostacyclin (PGI
2
) inherent to its molecular structure has long been a major limitation in assessing the natriuretic effect of this prostaglandin. The recent availability of the stable PGI
2
analogue iloprost now allows for a comparative study with prostaglandin E
2
(PGE
2
). In the present study conducted in six anesthetized dogs, the intrarenal effects of two consecutive doses (1 and 4 ng · kg
−1
· min
−1
) of PGE
2
on renal blood flow, glomerular filtration rate, and urinary sodium excretion were compared with the effects of two identical doses of iloprost. The selected doses of PGE
2
were those producing a maximal natriuretic and vasodilator response without affecting mean arterial pressure. A washout period was allowed between administration of PGE
2
and iloprost. PGE
2
infusion significantly increased fractional sodium excretion from 0.69±0.1 to 2.79±1.1% and 4.27±1.2%% (
P
<.05), respectively. These changes in fractional sodium excretion induced by PGE
2
were associated with significant increases in renal blood flow from 151.1±62 to 185±64.3 and 185.6±64.3 mL/min (
P
<.05), respectively; however, no significant alterations were seen in glomerular filtration rate, from 29.5±9.4 to 35.2±12.2 and 32.7±7.8 mL/min (NS), and mean arterial pressure, from 117.6±26 to 113.9±24.1 and 112.3±24.1 mm Hg (NS) during control and PGE
2
infusion. At identical doses, sequential infusion of PGI
2
had no effect on renal blood floww and glomerular filtration rate, producing natriuresis only at the highest dose, a fractional sodium excretion from 0.69±0.1 to 0.8±0.28 mm Hg (NS) and 1.05±0.34% (
P
<.05), respectively. In conclusion, the present study confirms that PGE
2
exerts a natriuretic effect during increases in renal blood flow. In contrast, PGI
2
had no hemodynamic effect, and the natriuresis was markedly blunted.
Sexual Dimorphism of Sodium-Sensitive Renal-Wrap Hypertension
Authors: Haywood Joseph R. , Hinojosa-Laborde Carmen
Published: June 2012

Abstract
One-kidney, figure-8 renal wrap or sham operation was performed on male and female rats to determine if a difference existed in the expression of hypertension between the sexes. Animals were prepared with radiotelemetry transmitters to monitor mean arterial pressure and heart rate continuously throughout an 8-week study. Dietary sodium content was changed during the post–renal-wrap period from normal (100 μmol/g chow) to high (2000 μmol/g chow) to low (<2 μmol/g chow) to assess sodium sensitivity. Both male and female rats experienced an increase in arterial pressure after the renal-wrap procedure; however, the hypertension was significantly attenuated in the females. High salt caused a further increase in both groups of rats that was again attenuated in the female rats. Low sodium diet reduced arterial pressure in all groups of rats. Heart rate was significantly elevated in the female rats during all dietary interventions. The data were fit to a cosine function to analyze circadian rhythm changes. An increase in the light/dark difference for arterial pressure in the hypertensive rats during high salt diet resulted in an increase in the circadian amplitude (range of the rhythm). In the normotensive rats fed a high salt diet, the arterial pressure acrophase (peak of rhythm) was delayed while the heart rate acrophase was shifted to an earlier time. These studies showed that female rats are protected against one-kidney, figure-8 renal-wrap hypertension and are less sensitive to the effects of sodium.