bluuebunny/crossref_metadata_2025 huggingface dataset:
Interaction of the sympathetic nervous system with vasopressin and renin in the maintenance of blood pressure.
Authors: Gavras H , Hatzinikolaou P , North W G , Bresnahan M , Gavras I
Published: June 2012

To evaluate the partial contributions and interaction of three vasopressor systems in blood pressure maintenance, nephrectomized rats and rats with intact kidneys were submitted sequentially to catecholamine depletion, elimination of vasopressin's vasoconstrictor action, and (for those with kidneys in situ) angiotensin blockade. Catecholamine depletion decreased blood pressure and stimulated vasopressin levels in all rats, but significantly more so in the anephric ones. Subsequent injection of an antagonist to the vasopressor effect of vasopressin produced a lasting fall of blood pressure in anephric rats, but only transient fall in those with intact kidneys. Infusion of teprotide--an angiotensin converting enzyme inhibitor--in the latter animals also produced transient blood pressure fall, but if this were followed by injection of the vasopressin antagonist, the pressure remained low for several hours. Blood pressure levels were closely correlated with those of plasma catecholamines throughout these maneuvers. Catecholamine levels were inversely correlated with those of plasma vasopressin, which were far greater in anephric rats through both stimulation and accumulation. Plasma renin activity was increasingly stimulated by falling blood pressure after each maneuver in rats with intact kidneys. Thus, it appears that in the resting state the sympathetic nervous system is more involved in the maintenance of blood pressure, whereas vasopressin and renin are important backup mechanisms.
Sympathetic system function and vascular reactivity in hypercalcemic patients.
Authors: Vlachakis N D , Frederics R , Valasquez M , Alexander N , Singer F , Maronde R F
Published: June 2012

To elucidate the pathophysiology of elevated blood pressure in hypercalcemic patients, we studied the plasma concentration of catecholamines and their major metabolites (as an index of sympathetic function) and the blood pressure response to norepinephrine infusion (vascular reactivity) in patients with primary hyperparathyroidism, in patients with primary hypertension, and in normal controls. In addition, we evaluated the hemodynamic response to calcium infusion in normotensive and hypertensive subjects. Plasma levels of both norepinephrine and epinephrine and the metabolites normetanephrine and dihydroxyphenyl-glycol were significantly higher in the hypercalcemic group than in the other two groups. Norepinephrine infusion increased blood pressure by 8.5 +/- 1.4 mm Hg in the control group, by 19 +/- 2 mm Hg in the hypercalcemic group and by 29 +/- 3 mm Hg in the primary hypertensive group. Infusion of calcium produced a significant rise in both systolic and diastolic blood pressures and in peripheral resistance in the hypertensives, whereas in the normotensive group only systolic blood pressure increased, associated with a rise in cardiac output. We conclude that the observed increased activity of the sympathetic nervous system in hypercalcemia could account for the elevation in blood pressure and the enhanced vascular reactivity could explain the hypertension in some patients with primary hyperparathyroidism.
Sodium-lithium exchange and sodium-potassium cotransport in human erythrocytes. Part 1: Evaluation of a simple uptake test to assess the activity of the two transport systems.
Authors: Duhm J , Göbel B O
Published: June 2012

A reliable and simple uptake test is proposed to assess the activity of the sodium lithium (Na+-Li+) countertransport and the sodium-potassium (Na+-K+) cotransport system of human erythrocytes. The test consists in measurement of phloretin-sensitive Li+ uptake from magnesium (Mg2+) media containing 2 mM Li+ and of furosemide-sensitive rubidium (Rb+) uptake from Na+ media containing 5 mM Rb+. Both Li+ and Rb+ are determined by atomic absorption spectrophotometry. The particular experimental conditions of the uptake assay are analyzed with respect to parameters that potentially affect the results, such as pH, cell volume, internal Na+, external Na+ and Rb+, presence of other ions, and concentration and protein-binding of furosemide, respectively. It is found that the activity of the two transport systems varies more than threefold among normotensive individuals, the activities in erythrocytes of each individual donor remaining stable within +/- 10% over more than two red cell life spans. The Li+ and Rb+ uptake rates are highly correlated to Li+ and K+ or Na+ release rates as determined by the methods of Canessa et al. and Garay et al. The test can thus be applied for routine screening in the search of "abnormalities" of red cell cation transport in hypertensive patients.
Sodium-lithium exchange and sodium-potassium cotransport in human erythrocytes. Part 2: A simple uptake test applied to normotensive and essential hypertensive individuals.
Authors: Duhm J , Göbel B O , Lorenz R , Weber P C
Published: June 2012

The sodium-lithium (Na+-Li+) exchange and sodium-potassium (Na+-K+) cotransport activities were assessed on erythrocytes of 38 normotensive individuals, 18 patients with well-established essential hypertension, and five renal hypertensive patients, by means of an uptake assay method. With both transport systems, no significant differences in mean values and variance were observed among the three groups. Four of six low-renin essential hypertensive patients exhibited some of the lowest exchange and cotransport rates obtained among all individuals examined. The activity of both transport systems was slightly lower in women than in men.
Vascular wall renin in spontaneously hypertensive rats. Potential relevance to hypertension maintenance and antihypertensive effect of captopril.
Authors: Asaad M M , Antonaccio M J
Published: June 2012

Relationships among systolic blood pressure (SBP), plasma renin activity (PRA), arterial renin concentrations (ARC), and venous renin concentrations (VRC) were examined in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats before and after treatment with captopril. The ARC was elevated in SHR relative to WKY whereas VRC was not. Similarly, ARC was related to SBP (r = 0.69, p less than 0.01) whereas PRA was not (r = 0.04). Captopril (100 mg/kg daily by mouth for 8 days) decreased blood pressure significantly in both SHR and WKY. PRA as well as ARC and VRC were all increased by captopril. Bilateral nephrectomy virtually eliminated PRA but ARC was not significantly reduced over a 24-hour period. Bilateral nephrectomy also markedly attenuated the acute antihypertensive effects of captopril in SHR; however, a modest effect was still apparent. It is suggested that ARC in SHR, being higher than in WKY, may play a role in the genesis or maintenance of hypertension in this model. Furthermore, the effects of captopril in both intact and nephrectomized SHR may be related to the ability of captopril to inhibit the vascular formation of angiotensin II. Finally, vascular renin is probably not renal in origin and responds to typical feedback inhibition as unmasked by captopril administration.
Blood pressure, heart rate, and plasma catecholamines in normal and hypertensive children and their siblings at rest and after standing.
Authors: McCrory W W , Klein A A , Rosenthal R A
Published: June 2012

Heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP), plasma norepinephrine (NE), and epinephrine (E) levels at rest and in response to orthostatic stress of quiet standing were compared in 19 subjects with borderline hypertension (BH) (SBP-135 mm Hg, DBP-80 mm Hg), nine with significant hypertension (SH) (SBP-150 mm Hg, DBP-95 mm Hg), 14 normotensive siblings (NS) of hypertensives (SBP-113 mm Hg, DBP-64 mm Hg), and 21 age-matched normotensive controls (NC) (SBP-116 mm Hg, DBP-61 mm Hg). Group resting plasma NE levels were significantly higher in BH (454 pg/ml, p less than 0.001 pg/ml) and SH (384 pg/ml, p less than 0.01 pg/ml) than in NC (281 pg/ml) or NS (309 pg/ml), and more than 2 SD above the NC mean value in 50% of BH, 28% of SH, and 7% of NS. Plasma E levels were similar. On standing, mean arterial pressure (MAP) rose 13.7 mm Hg in NC, 3.9 mm Hg in BH, and 2.8 mm Hg in NS, and fell 7.3 mm Hg in SH. These differences reflect the frequent occurrence of hypotensive responses in study group subjects, which were not observed in NC. The mean rise in plasma NE with standing was blunted in hypertensives, increasing 40% to 50% compared with 95% in NC. In BH and NS, SBP was positively correlated with plasma NE levels at rest and with standing. These observations offer support for the hypothesis that altered adrenergic sympathetic nervous system (SNS) activity is present in a subgroup of young hypertensives and can be a contributing factor to their hypertension. Findings of similar SNS activity in some normotensive siblings suggest that genetic factors might be involved.
Red cell lithium-sodium countertransport and sodium-potassium cotransport in patients with essential hypertension.
Authors: Adragna N C , Canessa M L , Solomon H , Slater E , Tosteson D C
Published: June 2012

Alterations in sodium countertransport and cotransport have been reported in red cells of patients with essential hypertension. We have investigated the relationship between these two systems by performing simultaneous measurements of the maximal rates of lithium-sodium (Li1-Na0) countertransport and outward sodium-potassium (Na-K) cotransport in red cells from normotensive and hypertensive subjects. Li1-Na0 countertransport was assayed by measuring the Na0-stimulated Li efflux from cells loaded to contain 10 mmoles Li per liter of cells by incubation in isotonic LiCl. Na-K cotransport was assayed by measuring the furosemide-sensitive component of Na and K efflux into magnesium-sucrose medium from cells loaded by the p-chloromercuribenzene sulfonic acid (PCMBS) procedure to obtain 50 mmoles of both ions per liter of cells. The mean values (+/- SE) for 16 normotensives and 22 hypertensives were (mmole/liter cells x hour): Na countertransport = 0.29 +/- 0.02 vs 0.51 +/- 0.03 (p less than 0.001); Na cotransport = 0.30 +/- 0.03 vs 0.51 +/- 0.05 (p less than 0.005); and K cotransport = 0.34 +/- 0.03 vs 0.60 +/- 0.04 (p less than 0.005). Li1-Na0 countertransport correlated significantly with Na cotransport (r = 0.50, n = 38, p less than 0.005) and K cotransport (r = 0.57, p less than 0.005). This observation suggests that both transport systems are somehow regulated to be more active in this group of hypertensive patients. The increased cotransport in hypertensive patients is also apparent from two other measurements of Na and K fluxes in red cells suspended in Na medium. First, the furosemide-sensitive net Na efflux into Na medium was (mean +/- SE) 0.25 +/- 0.05 in 10 normotensive subjects and 0.50 +/- 0.09 in 12 hypertensive patients. Second, the furosemide-sensitive net K efflux into Na medium was (mean +/- SE) 0.25 +/- 0.04 in 13 normotensive subjects and 0.43 +/- 0.04 in 16 hypertensive patients (p less than 0.005). We conclude that mean values for both Na countertransport and Na-K cotransport are significantly higher in the group of hypertensives than in the group of normal control subjects.
Heart size in inbred strains of rats. Part 1. Genetic determination of the development of cardiovascular enlargement in rats.
Authors: Tanase H , Yamori Y , Hansen C T , Lovenberg W
Published: June 2012

The heart and aorta weights in 23 strains of rats and the four-way cross generation among the M520/N, SHRSP/N, SHR/N, and WKY/N strains were investigated in relation to their blood pressure in an attempt to characterize cardiovascular enlargement (increased weight of heart and aorta) from a genetic aspect. The distribution of blood pressure in these strains at 10 weeks of age was clearly divided into hypertensive and normotensive groups. In the hypertensive group, heart weight increased in proportion to blood pressure. In contrast, there was no relationship between blood pressure and heart weight in the normotensive group in spite of large strain differences in heart weights. The result of variance analysis exhibited a significant strain difference in heart weight, and the degree of genetic determination was estimated to be 65%-75%. A similar genetic influence was apparent for normotensive strains excluding hypertensive strains. The distribution of blood pressures in the four-way cross generation showed the segregation of three phenotypes consisting of normotensive, intermediate and hypertensive groups. A large variability was seen in heart weight of each group. However, the increase in average heart weight of these three groups was very small. The degree of genetic determination from the cross analysis was estimated to be 45%-65%. These results indicate that heart weight is a highly heritable trait, and that the effect of genetic factors on cardiac enlargement is larger than that of blood pressure. A similar result was obtained for the aorta weight. However, the effect of genetic factors was less important for aorta weight than for heart weight since the degree of genetic determination was estimated to be 45%-65% from the strain comparison and 35%-60% from the cross analysis.
Preeclampsia -- a state of prostaglandin deficiency? Urinary prostaglandin excretion, the renin-aldosterone system, and circulating catecholamines in preeclampsia.
Authors: Pedersen E B , Christensen N J , Christensen P , Johannesen P , Kornerup H J , Kristensen S , Lauritsen J G , Leyssac P P , Rasmussen A , Wohlert M
Published: June 2012

Urinary excretion of prostaglandin E2 (PGE2) and F2 alpha (PGF2 alpha), plasma concentrations of renin, aldosterone, norepinephrine (NE) and epinephrine (E) were determined during pregnancy, 5 days, 3, and 6 months after delivery in preeclampsia, normotensive pregnant, and nonpregnant control subjects. The PGE2 was higher in normotensive pregnant control subjects than in nonpregnant subjects. In preeclampsia, PGE2 was reduced to nonpregnant level. PGF2 alpha was the same in preeclampsia and in normotensive pregnancy, but elevated when compared to the normotensive nonpregnant control group. Plasma concentrations of renin and aldosterone were increased during pregnancy, but considerably less in preeclampsia than during normotensive pregnancy. NE and E were the same as in nonpregnant subjects during both hypertensive and normotensive pregnancy. All parameters were normal 3 months after delivery. There were no correlations between PGE2, PGF2 alpha, plasma concentrations of renin, aldosterone, NE, or E and blood pressure level in third trimester either in preeclampsia or in normotensive pregnancy. PGE2 was positively correlated to plasma concentrations of renin. It is suggested that the lack of renal PGE2 in preeclampsia might be responsible for the decrease in renal blood flow and sodium excretion. It is hypothesized that preeclampsia is a state of prostaglandin deficiency. The changes in the renin-aldosterone system may be secondary to changes in prostaglandin concentration both in preeclampsia and normotensive pregnancy.
Accuracy of auscultatory blood pressure measurements in hypertensive and obese subjects.
Authors: Nielsen P E , Larsen B , Holstein P , Poulsen H L
Published: June 2012

In 59 treated or untreated hypertensive subjects and 52 obese subjects (normotensive or hypertensive), intraarterial blood pressure (BP) was compared to simultaneous auscultatory measurements. In the hypertensive group, arm circumference was less than 35 cm compared to over 35 cm in the obese subjects. The occluding cuffs were 12 x 35 cm and 15 x 43 cm respectively. Mean difference between auscultatory and intraarterial systolic BP (SBP) was among the hypertensive -- 8.8 mm Hg (SDDIFF 9.0 mm Hg, range + 13/ - 28) and among the obese - 3.1 mm Hg (SDDIFF 13.8 mm Hg, range + 19/ - 49). Mean difference auscultatory-intraarterial diastolic BP (DBP) Phase V was among the hypertensive patients + 10.8 mm Hg (SDDIFF 6.8 mm Hg, range + 29/ - 8), and among the obese + 5.5 mm Hg (SDDIFF 7.3 mm Hg, range + 20/ - 10). Thus, a 15 x 43 cm cuff used in obese subjects with an arm circumference exceeding 35 cm gave quite as reliable measurements as a 12 x 35 cm cuff used in hypertensive subjects with "normal" dimension of the upper arm (less than 35 cm). It is emphasized that there is a wide scatter in the interindividual differences, and it is argued that a comparison between auscultatory and intraarterial BP should be performed in patients with poorly controlled hypertension.
Enhanced NE uptake by isolated hypothalamic storage vesicles of hypertensive rats.
Authors: Rho J H , Newman B L , Alexander N , Hough K L
Published: June 2012

The in vitro uptake of 3H-NE by storage vesicles from the hypothalamus of age-matched spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats has been studied using a new reliable procedure for the isolation of biochemically active storage vesicles. In each of 13 paired studies, done in triplicate, storage vesicles of SHR took up more 3H-NE than those of WKY. (The mean difference was 37% more uptake by SHR.) Electron-microscopic examination of normotensive samples showed a concentration of intact synaptic vesicles; whereas SHR subfractions were composed of fragmented membranes that resembled swollen, distorted vesicles. These findings in the brain tissues of SHR parallel our previous results found in SHR peripheral tissues. Taken together, we interpret the results to indicate that the membranes of synaptic vesicles of SHR are altered structurally and biochemically.
Renal afferent arteriole in the spontaneously hypertensive rat.
Authors: Gattone V H , Evan A P , Willis L R , Luft F C
Published: June 2012

We conducted morphometric studies on the afferent arteriole of spontaneous hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats to gain a better understanding of its changes with the development of hypertension. Differences may be related to the SHRs' increased renal vascular resistance. Methacrylate vascular casts were made of the renal vasculature after perfusion fixation with glutaraldehyde. These vascular casts were then examined and measurements made with the scanning electron microscope. Results from this examination of the scanning electron microscope demonstrated a smaller afferent arteriolar diameter in the SHR, compared to the WKY, for both the inner and outer cortical glomeruli. This difference was seen in the 6-week-old SHR, prior to a statistically different blood pressure from the WKY controls, as well as in the 12-week-old hypertensive SHR. However, this afferent diameter difference between rat strains was more pronounced in rats at 12 weeks of age. The tapering of the afferent arteriole (difference between proximal and distal afferent diameters) was greater in the 12-week-old SHR than in the age-matched WKY or 6-week-old SHR. We conclude that the smaller caliber afferent arterioles of the SHR may predispose and play a role in the pathogenesis of the subsequent hypertension. The increased afferent arteriolar tapering seen in the hypertensive SHR relates to the already present increased blood pressure. Wall thickness/radius ratios are not different between rat strains (SHR and WKY) at either 6 or 12 weeks of age. These results suggest increased vascular constriction or hypoplastic vessels as the cause of the smaller caliber vessels in the SHR rather than increased wall thickness.
Plasma catecholamines and essential hypertension. An analytical review.
Authors: Goldstein D S
Published: June 2012

Of 78 comparative studies of plasma catecholamines in patients with essential hypertension and in normotensive controls, most reported higher catecholamine levels in the hypertensives, although only about 40% of the studies were positive (reporting statistically significant hypertensive-normotensive differences). Although there was dramatic variability in catecholamine values within and across studies, virtually all studies of norepinephrine in young, consistently hypertensive patients were positive. The likelihood that a study was positive with respect to norepinephrine was independent of the likelihood with respect to epinephrine, so that total catecholamine values, or else the sum of norepinephrine plus epinephrine, differentiated hypertensives from normotensives to a greater extent than levels of either substance alone. The preponderance of literature on the subject supports the hypothesis that increased plasma catecholamine concentrations occur in some patients with essential hypertension. Elevated plasma norepinephrine in relatively young, established hypertensive patients is consistent with a pathophysiologic role for increased sympathetic neural activity in this subgroup.
Relationship of 19-nor-deoxycorticosterone to other mineralocorticoids in low-renin hypertension.
Authors: Griffing G T , Dale S L , Holbrook M M , Melby J C
Published: June 2012

A number of mineralocorticoids have been proposed as etiologic factors in low-renin hypertension. In this study, urinary free 19-nor-deoxycorticosterone (UF 19-nor-DOC) was compared to other mineralocorticoids--aldosterone, deoxycorticosterone (DOC), and 18-OH-DOC, in 11 low-renin hypertensive patients on a controlled diet in a metabolic unit. Results demonstrated that both UF 19-nor-DOC and tetrahydro-DOC (TH-DOC) excretion were elevated (2086 +/- 926, nl = 339-579 ng/day, and 18 +/- 7, nl = 5-15 mcg/day, respectively), and positively correlated (r = 0.95). Neither 18-OH-DOC nor aldosterone secretion rates were elevated, and neither of these hormones correlated with UF 19-nor-DOC, with exception of the supine plasma aldosterone (SPA) (r = 0.86). In conclusion, both UF 19-nor-DOC and TH-DOC were increased and positively correlated in the present series of hypertensives. This association is possibly indicative of a precursor-product relationship between DOC and 19-nor-DOC. 19-Nor-DOC, furthermore, correlated with supine plasma aldosterone (SPA), which could, in part, reflect their shared adrenocorticotropic hormone (ACTH) dependence.
Potassium infusion attenuates avoidance-saline hypertension in dogs.
Authors: Anderson D E , Kearns W D , Worden T J
Published: June 2012

Previous studies have shown that a combination of avoidance conditioning schedules and increased intake of salt and water results in progressive hypertension in dogs within 14 days. The present experiments investigated the effects of increasing potassium intake upon blood pressure and heart rate of dogs made hypertensive by avoidance conditioning and salt-water loading. Two daily 30-minute sessions of free-operant avoidance conditioning were presented for 36 days during which isotonic saline was continuously infused into the arterial circulation (1.2 liters/day; 185 mEq Na+). Daily mean levels of systolic (22 +/- 5 mm Hg) and diastolic (12 +/- 4 mm Hg) pressure increased progressively in each dog during Days 1-14. Infusion of potassium chloride (100 mEq/day) from Days 15-28 resulted in progressive decreases in daily mean levels of systolic (-11 +/- 2 mm Hg) and diastolic (-8 +/- 1 mm Hg) pressure in each dog over this period. From Day 29-36, systolic (8 +/- 1 mm Hg) and diastolic (5 +/- 1 mm Hg) pressure increased. Normotensive dogs not on the avoidance schedule showed no change in arterial pressure in response to 14 days of potassium chloride infusion. These experiments show that the level of potassium, as well as sodium, intake significantly determines blood pressure levels in this form of experimental hypertension.
Thallium uptake by canine iliac arteries.
Authors: Rangachari P K , Grover A K , Daniel E E
Published: June 2012

Most of the thallium uptake by canine iliac arteries (70%) was inhibited by ouabain. The component sensitive to ouabain was significantly increased by incubating tissues in K+-free solution and reduced by low temperatures, metabolic inhibitors, and loading with lithium. The apparent Km for thallium for the ouabain-sensitive uptake was 0.47 +/- 0.046 mM. External K+ inhibited thallium uptake and the apparent Ki was estimated to be 6.5 mM. Thallium thus appears to have a greater affinity for the ouabain-sensitive components. The residual component of thallium uptake was unaffected by maneuvers that affected the ouabain-sensitive uptake, which thus appears to be a suitable indicator of Na+ pump activity in vascular smooth muscle.
Elevated plasma catecholamines in hypertensives with primary glomerular diseases.
Authors: Ishii M , Ikeda T , Takagi M , Sugimoto T , Atarashi K , Igari T , Uehara Y , Matsuoka H , Hirata Y , Kimura K , Takeda T , Murao S
Published: June 2012

Supine plasma concentration of norepinephrine (PNE), epinephrine (PE), and aldosterone (PA), plasma renin activity (PRA), and blood volume (BV) were measured in 25 normotensive and 11 hypertensive patients with biopsy-proven glomerulonephritis who had serum creatinine concentrations of less than 1.6 mg/dl, and in 20 normotensive control subjects. PNE and PE were measured according to the trihydroxyindol method using high pressure liquid chromatography. Renal clearances of p-aminohippurate (CPAH) and endogenous creatinine (Ccr) were also determined. Age, BV, and 24-hour urinary excretion of sodium were not significantly different in the three groups. Although all the measured variables were comparable between the control subjects and the normotensive nephritic patients, blood pressure, PNE, PE, PRA, and PA were significantly higher and CPAH and Ccr were significantly lower in the hypertensive nephritic patients than in the normotensive nephritic patients or the control subjects. In the pooled nephritic patients, mean blood pressure was significantly correlated with PNE (r = 0.76, p less than 0.001), PE (r = 0.34, p less than 0.05), PRA (r = 0.33, p less than 0.05), PA (r = 0.40, p less than 0.05) and CPAH (r = -0.51, p less than 0.01). Highly significant positive correlation was also observed between PNE and systolic pressure (r = 0.63, p less than 0.001) or diastolic blood pressure (r = 0.78, p less than 0.001). The results suggest that deterioration of renal function is an important factor in the development of hypertension even in non-azotemic patients with glomerulonephritis, and that increased activities of the sympathetic nervous system and the renin-aldosterone system participate, in part, in elevating blood pressure in the hypertensive nephritic patients. Mechanisms involved in the elevation of plasma concentrations of catecholamines and renal effects on the plasma catecholamines remain to be elucidated.
Altered vascular reactivity and baroreflex sensitivity induced by chronic central administration of captopril in the spontaneously hypertensive rat.
Authors: Berecek K H , Okuno T , Nagahama S , Oparil S
Published: June 2012

Previous studies from our laboratory have shown that chronic intracerebroventricular administration of captopril attenuates the development of hypertension in the spontaneously hypertensive rat of the Okamoto strain (SHR) without altering sodium and water balance, plasma renin, or sympathoadrenal activities. To determine whether the depressor effect of intracerebroventricular captopril was associated with an alteration in peripheral vascular reactivity and/or baroreflex sensitivity, vascular reactivity to phenylephrine and vasopressin was assessed in renal, mesenteric, and hindquarter vascular beds using pulsed Doppler flow probes. Captopril was infused into the jugular vein or lateral ventricle of male SHR and Wistar-Kyoto (WKY) rats for 4 weeks (osmotic mini pump, 1.25 micrograms/0.5 microliter/hr). Control SHR or WKY received intracerebroventricular infusions of vehicle. Four weeks of captopril decreased arterial pressure in both SHR and WKY. In response to phenylephrine and vasopressin, SHR and WKY treated with intracerebroventricular captopril showed significantly attenuated increases in arterial pressure and vascular resistance in comparison to either vehicle-treated rats or rats receiving intravenous captopril. Reflex decreases in heart rate in response to phenylephrine were also greater in SHR and WKY treated with intracerebroventricular captopril than in the other rat groups. Neither vascular reactivity nor baroreflex sensitivity was altered in rats treated with intravenous captopril. We conclude that the depressor effect of captopril involves a blunting of vascular reactivity to vasoconstrictors and a potentiation of the baroreflex.
Acute effects of metoprolol on muscle sympathetic activity in hypertensive humans.
Authors: Sundlöf G , Wallin B G , Strömgren E , Nerhed C
Published: June 2012

Recordings of multiunit sympathetic activity were made from muscle branches of the peroneal nerve in eight previously untreated subjects with essential hypertension during intravenous administration of the cardioselective beta-adrenoceptor antagonist, metoprolol. Intraarterial blood pressure and central venous pressure were monitored simultaneously. After metoprolol, heart rate fell and central venous pressure increased in all subjects. Blood pressure increased in some subjects and decreased in others whereas the rate of rise of the systolic pulse wave regularly decreased. Sympathetic activity, discharged in pulse synchronous bursts of action potentials, was quantitated by counting the number of bursts and their amplitudes in the mean voltage neurogram. In all subjects, the average diastole was associated with outflow of more sympathetic impulses after metoprolol than before. Total sympathetic activity (expressed as bursts/min multiplied by mean burst strength) also increased after the drug. The mechanism behind the increase of sympathetic activity may be either a direct central nervous effect or a reflex effect elicited from arterial baroreceptors or cardiac receptors.
Role of dietary potassium in the treatment of hypertension.
Authors: Treasure J , Ploth D
Published: June 2012

This review summarizes the historical development and recent resurgence of interest in dietary potassium as a factor in hypertension. Some epidemiologic evidence has suggested that potassium intake by humans may be inversely related to the level of arterial blood pressure. Other studies have suggested that a marked reduction in the Na+/K+ ratio of the human diet reduces the blood pressure of normotensives. Further, the administration of high potassium diets has resulted in a lowering of blood pressure in some animal models of hypertension. Several possible mechanisms for this putative antihypertensive effect are evident. Some observations suggest that potassium could act as a diuretic agent and thereby reduce extracellular fluid volume, which in turn could result in decreased blood pressure. An alternative mechanism of action is that potassium may alter the activity of the renin-angiotensin system and reduce angiotensin influences on vascular, adrenal, or renal receptors. Other evidence supports the possibility that potassium modifies central or the peripheral neural mechanisms that regulate blood pressure. In addition, high potassium diets could reduce blood pressure by relaxing vascular smooth muscle and reducing peripheral vascular resistance directly. Although diets high in potassium content do appear to modify arterial blood pressure under some circumstances, particularly in salt-dependent hypertension, a high potassium intake has not always attenuated blood pressure in all models examined. Further, evaluation of these data do not allow definite conclusions regarding a common mechanism through which potassium exerts these effects.
Cardiovascular counterregulation during sympathetic inhibition in normal subjects and patients with mild hypertension.
Authors: Weidmann P , Beretta-Piccoli C , Link L , Bianchetti M G , Boehringer K , Morton J J
Published: June 2012

The influence of agents that inhibit sympathetic nerve activity on cardiovascular responsiveness as related to major pressor factors has been unclear. Therefore, these components were evaluated in 11 normal subjects and 13 patients with mild essential hypertension before and after 4 weeks of sympathetic neuron blockade with the agent debrisoquine. In these normal and mildly hypertensive subjects, sympathetic neuron blockade caused approximately similar decreases in urinary and supine or upright plasma norepinephrine (NE) levels (average changes in the two groups, -41% and -45%, respectively; p less than 0.05 to less than 0.005), the chronotropic dose of isoproterenol (-45% and -38%), and the NE pressor dose (-47% and -51%, p less than 0.01), while the relationship between NE-induced changes in blood pressure and concomitant plasma NE concentrations was displaced to the left (p less than 0.01). Supine heart rate was also lowered (-10% and -8%, p less than 0.05). Compared to the orthostatic variations during placebo conditions, mild postural decreases in blood pressure were apparent in both the normal and hypertensive groups (-8% and -7.5%). However, supine blood pressure was unchanged following debrisoquine treatment. Other parameters were also not consistently changed, such as total blood volume, exchangeable body sodium, urinary electrolytes, plasma epinephrine, renin, and angiotensin II (AII) levels, the pressor dose of infused AII, and the relationship between AII-induced changes in blood pressure and plasma AII measured before and during AII infusion. These findings demonstrate that the reduction in sympathetic outflow during sympathetic neuron blockade may elicit a hyperresponsiveness of alpha- and beta-adrenergic receptors that is equal in normal subjects and patients with mild essential hypertension.
Effects of graded renal artery constriction on blood pressure, renal artery pressure, and plasma renin activity in Goldblatt hypertension.
Authors: Murphy W R , Coleman T G , Smith T L , Stanek K A
Published: June 2012

One-kidney, one clip (1K1C) and two-kidney, one clip (2K1C) Goldblatt hypertension was produced in rats by placing 0.30, 0.25, or 0.20 mm silver clips on the left renal artery. Mean arterial pressure (MAP) and plasma renin activity (PRA) were measured in conscious rats 24 to 28 days after clipping. The MAP in control rats (n = 38) was 116 +/- 1 mm Hg (mean +/- SEM). The 0.30, 0.25, and 0.20 mm clips produced MAPs of 133 +/- 2, 161 +/- 5, and 189 +/- 5 mm Hg, respectively, in 1K1C rats, and 123 +/- 2, 129 +/- 3, and 172 +/- 5 mm Hg in 2K1C rats (n = 17-20). When 1K1C and 2K1C groups were compared, MAP was significantly greater in 1K1C rats at all clip sizes. No treatment group's PRA was different than control (4.8 +/- 0.4 ng AI/ml/hr), except for the 0.20 mm 2K1C rats (16.2 +/- 3.1 ng AI/ml/hr). Renal artery pressure (RAP) was measured in another series of experiments and was not different from control in all but the 0.20 mm 1K1C rats. With identical clip sizes, 2K1C rats showed smaller pressure gradients than 1K1C across the clips: 0.30 mm, 8.5 +/- 1.7 vs 10.7 +/- 1.9 mm Hg; 0.25 mm, 16.5 +/- 1.2 vs 42.1 +/- 7.5 mm Hg; 0.20 mm, 51 +/- 5.3 vs 79.1 +/- 5.7 mm Hg (n = 8-12). Therefore, both the increase in MAP and the pressure gradient across the clip were greater in the 1K1C rats at every clip size.(ABSTRACT TRUNCATED AT 250 WORDS)
Primary hyperaldosteronism in childhood due to unilateral macronodular hyperplasia. Case report.
Authors: Oberfield S E , Levine L S , Firpo A , Lawrence D , Stoner E , Levy D J , Sen S , New M I
Published: June 2012

We present the first report of primary hyperaldosteronism in childhood due to unilateral macronodular hyperplasia. A 10-year-old white boy with severe hypertension (150/100 mm Hg), hypokalemia (1.4 mEq/liter), and suppressed plasma renin activity (PRA) (less than 0.1 ng/ml/hr) demonstrated fixed PRA and aldosterone (aldo) levels that did not change with alteration of dietary sodium. The paradoxical decrease in serum aldo on assumption of upright posture suggested a tumor. Prolonged ACTH administration produced a continuous rise in blood pressure, but a transient rise in aldo. A minimal decrease in urinary aldo during dexamethasone administration was noted, excluding dexamethasone-suppressible hyperaldosteronism. Blood pressure normalized with spironolactone. Computerized transaxial tomography, iodocholesterol scanning, and adrenal venography were not diagnostic of a discrete adrenal lesion. Although hyperplasia is more common than an adenoma as a cause of hyperaldosteronism in childhood, a tumor was predicted, since adrenal vein hormone sampling with ACTH stimulation lateralized aldosterone secretion unequivocally to the left adrenal gland. However, left adrenalectomy revealed macronodular hyperplasia. Postoperatively, there was reversal of hypertension, hypokalemia, and hyperaldosteronism. Thus, in childhood, unilateral hypersecretion of aldosterone may result from nodular hyperplasia, rather than a discrete adenoma.
Microvascular adaptation in the cerebral cortex of adult spontaneously hypertensive rats.
Authors: Harper S L , Bohlen H G
Published: June 2012

The purpose of this study was to determine the microvascular characteristics that cause cerebral cortical blood flow autoregulation to shift to a higher range of arterial pressures during established hypertension in spontaneously hypertensive rats (SHR). An open-skull technique with constant suffusion of artificial cerebrospinal fluid (PO2 = 40-45 mm Hg, PCO2 = 40-45 mm Hg, pH = 7.35-7.45) was used to view the parietal cortex of 18- to 21-week-old SHR and Wistar Kyoto (WKY) normotensive control rats. The resting inner diameters of first (1A)-, second (2A)-, and fourth (4a)-order arterioles were significantly (p less than 0.05) smaller, and the wall thickness/lumen diameter ratios were significantly (p less than 0.05) larger in SHR compared to WKY. Only 1A and 4A has significantly (p less than 0.05) increased vessel wall cross-sectional area in SHR. At the resting mean arterial pressures of WKY and SHR, the passive (10(-4) M adenosine, topical) diameters of comparable types of arterioles were not significantly different (p greater than 0.05). At reduced arterial pressures, however, the arterioles in SHR had smaller maximum diameters than in WKY. Cortical blood flow in WKY and SHR was constant at arterial pressures from 70-150 mm Hg and 100-200 mm Hg, respectively. Resting arteriolar pressures in 1A, 2A, and 3A of SHR were substantially and significantly (p less than 0.05) elevated, although pressures in the smallest arterioles and venules of WKY and SHR were similar. Therefore, it is possible that cerebral capillary pressure is only slightly elevated, if at all, in SHR as a result of the vasoconstriction. The number of arterioles per unit area of brain surface at rest was equal in WKY and SHR. In addition, the number of vessels was equal in WKY and SHR during maximal dilation, and neither type of rat demonstrated an opening of previously closed vessels upon maximum dilation. Therefore, the cerebral arteriolar constriction in SHR, which was probably potentiated by vessel wall hypertrophy of the largest and smallest arterioles, was the major contributor to an upward shift in the autoregulatory range, the protection of exchange vasculature pressures, and the increase in vascular resistance.
Differential effect of salt loading on sodium and lithium excretion in Dahl salt-resistant and -sensitive rats.
Authors: Roos J C , Kirchner K A , Abernethy J D , Langford H G
Published: June 2012

Fractional excretion of lithium, as a marker for proximal sodium reabsorption, was determined in normotensive Dahl S rats (susceptible to NaCl hypertension) and Dahl R rats (resistant to NaCl hypertension) before and following an acute sodium load. Baseline mean arterial pressures, inulin clearances, sodium excretion rates, and fractional lithium clearances were not different between the R and S rats. Following the salt loading and despite similar mean arterial pressures and degree of volume expansion, the glomerular filtration rate, urinary flow rates, and absolute sodium excretion rates were greater in R than S rats. The fractional excretion of lithium was also greater in R than S rats. These data demonstrate that, at equal mean arterial pressures, Dahl S rats have a reduced capacity for sodium excretion, and that this defect is present prior to the development of hypertension. Furthermore, the observation that these animals also have a lower fractional lithium excretion during volume expansion suggests that salt loading reduces proximal tubule reabsorption to a lesser extent in Dahl S than R rats. These data suggest that the subnormal sodium and water excretion observed after sodium loading in S rats may be partially due to an abnormality in proximal tubule sodium handling.
Rat thymocyte sodium transport. Effects of changes in sodium balance and experimental hypertension.
Authors: Bradlaugh R , Heagerty A M , Bing R F , Swales J D , Thurston H
Published: June 2012

The wide range of membrane electrolyte transport abnormalities associated with experimental, genetic, and essential hypertension may either reflect an underlying global change in the cell membrane or may be directly related to the underlying disturbance that causes hypertension or to changes in sodium balance. To investigate this further, we studied sodium transport and intracellular electrolyte composition in the thymocytes of normal rats undergoing salt loading or depletion, and in rats with renovascular, mineralocorticoid, or spontaneous hypertension compared to appropriate age-matched normotensive control rats. In normotensive rats, although there was no significant difference between the blood pressures at the two extremes of sodium balance, sodium loading caused a nonsignificant rise in sodium transport, whereas sodium depletion was associated with a significant fall in sodium transport and intracellular sodium. When cells from salt-loaded or normal animals were incubated in a medium containing their own serum, sodium transport was slightly stimulated in both, but there was no significant difference in the sodium efflux-rate constant of thymocytes obtained from rats on the normal as opposed to the high salt intake. Compared to normotensive rats, there was no significant change in the sodium efflux-rate constant in any of the hypertensive rat models studied. However, the sodium efflux-rate constant fell with age in both the spontaneously hypertensive and Wistar-Kyoto normotensive rats. The present studies show that dietary sodium intake and aging had considerable effects on rat thymocyte sodium transport, but neither of these changes was related to a change in blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Evidence for the existence of vascular alpha 2-adrenergic receptors in humans.
Authors: Goldberg M R , Robertson D
Published: June 2012

Many studies have suggested that alpha-adrenergic receptors on vascular smooth muscle are heterogeneous and that both alpha 1- and alpha 2-adrenergic receptors can cause vasoconstriction when stimulated. We explored this hypothesis in normal humans by comparing the capacity of yohimbine, an alpha 2-adrenergic receptor antagonist, and prazosin, an alpha 1-adrenergic receptor agonist, with differentially blocked pressor responses to phenylephrine, an alpha 1-adrenergic receptor agonist, and epinephrine, a nonselective alpha-agonist. We studied these responses in normal male volunteers who had been pretreated with propranolol (80 mg orally every 8 hours for 5 days) to obviate stimulation of beta-receptors by either agonist. We found differential effects of the antagonists on responses to the two agonists. Yohimbine induced a 3.1-fold (+/- 0.5) shift in the dose of epinephrine, which raised blood pressure 25 mm Hg, and only a 1.9-fold (+/- 0.2) shift in the response to phenylephrine (p less than 0.01). Prazosin induced a 2.4-fold (+/- 0.5) shift in the responses to epinephrine and a 4.5-fold (+/- 1.2) shift in the response to phenylephrine (p less than 0.05). These data are consistent with the notion that alpha-adrenergic receptors in the human vasculature are not homogeneous, but rather may be subdivided into at least two subtypes, one resembling alpha 1-adrenergic receptors and the other resembling alpha 2-adrenergic receptors.
Influence of androgen on translatable renin mRNA in the mouse submandibular gland.
Authors: Pratt R E , Dzau V J , Ouellette A J
Published: June 2012

In mature outbred Swiss male mice, submandibular gland renin enzyme activity is 4- and 10-fold higher than in glands of prepubescent males and mature females, respectively. Levels of translatable renin mRNA have been studied in mouse submandibular gland during postnatal development and following administration of testosterone. The [35S]methionine-labeled cell-free translation products directed by male glandular mRNA contain a 47 +/- 2kd renin precursor that is not detected in products coded by prepubescent male or female gland mRNA. This cell-free synthesized precursor is detected immunochemically only in the translation products of gland mRNA from males of 33 days or older and from females receiving testosterone administration, a pattern consistent with the measurements of renin enzyme activity. This increase in biologically active renin mRNA is a selective one, since unfractionated male and female mRNAs have similar overall nucleotide sequence complexity corresponding to 1% of mouse single copy DNA. The cDNA transcribed from male gland mRNA reacts 5- and 10-fold faster with the template mRNA than with female or prepubescent male gland mRNA, respectively, which indicates that the male gland contains abundant nucleotide sequences that exist at low concentration in the female or prepubescent male. Selective hybrid arrested translation confirms that the levels of renin mRNA are lower in the glands of prepubescent males than in those of the mature males. These data indicate that the regulation of renin enzymatic activity by androgens is mediated by an increase in the levels of translatable renin mRNA both during postnatal development and after testosterone administration.
Effects of captopril on vascular noradrenergic transmission in SHR.
Authors: Eikenburg D C
Published: June 2012

The effects of captopril, 3 and 10 mg/kg, on vascular noradrenergic transmission were examined in vivo in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). These experiments were performed on mesenteric vascular beds perfused in situ. In WKY, 3 mg/kg captopril failed to significantly lower mean arterial blood pressure (MAP) and also failed to have a significant effect on the frequency-response curve to sympathetic nerve stimulation or dose-response curve to norepinephrine (NE) in the mesentery of WKY. In SHR mesentery, 3 mg/kg captopril failed to alter the frequency response curve or NE dose-response curve, while it significantly lowered MAP. The higher dose of captopril, 10 mg/kg, also failed to lower MAP in WKY mesentery, although it caused some reduction in pressor responses to sympathetic nerve stimulation and NE. In SHR mesentery, 10 mg/kg captopril significantly lowered MAP and reduced pressor responses to both nerve stimulation and NE. It should be noted, however, that captopril lowered responses to nerve stimulation and NE to a similar degree in both SHR and WKY, and there was no indication of a prejunctional action on vascular noradrenergic transmission. In conclusion, although captopril was more effective in lowering MAP in SHR than in WKY, no evidence was found for significantly greater facilitation of vascular sympathetic neurotransmission by endogenous angiotensin II in SHR than in WKY, and most of the actions of captopril on vascular neurotransmission appeared to be postjunctional in nature and unrelated to either the renin-angiotensin system or the kallikrein-kinin system.