bluuebunny/crossref_metadata_2025 huggingface dataset:
Dietary sodium and potassium-induced transient changes in blood pressure and catecholamine excretion in the Sprague-Dawley rat.
Authors: Battarbee H D , Dailey J W , Meneely G R
Published: June 2012

When Sprague-Dawley derived rats were changed from a chow type diet to a moderately high sodium diet, rapid transient changes in blood pressure (BP) and catecholamine excretion were observed. After 1 dietary week, BP increased from 122 +/- .1 mm Hg to approximately 145 mm Hg (p less than 0.001), and there was a concomitant 20% reduction in urinary norepinephrine (UNEV) and epinephrine (UEV) excretion (p less than 0.05). Heart rates were reduced (p less than 0.05). These data suggest that sodium-induced increases in BP were initially associated with suppressed sympathetic nervous system activity. During dietary Weeks 2 and 3, some animals had a persistent moderate elevation in BP (BP less than or equal to 150 mm Hg), while others developed more severe increases. UNEV in moderately hypertensive animals returned to control levels during this period; but UEV and heart rates remained suppressed. UNEV in severely hypertensive animals exceeded (13% +/- 3%, p less than 0.05) that of controls. This increase coincided with their most severe hypertension (171 +/- 1 mm Hg, p less than 0.001). UE values and heart rate data indicate that systemic adrenergic tone was likely suppressed at this time and that the increased UNEV was renal in origin. By dietary Week 4, the BP of severely hypertensive animals had begun to fall, and indices of sympathetic nervous system tone were indistinguishable among all groups. Inclusion of a dietary potassium supplement ameliorated the development of hypertension only in those animals that became severely hypertensive, and appeared to prevent the early suppression of indices of sympathetic activity.
Altered turnover of polyphosphoinositides in the erythrocyte membrane of the spontaneously hypertensive rat.
Authors: Koutouzov S , Marche P , Girard A , Meyer P
Published: June 2012

The metabolism of inositol phospholipids of the erythrocyte membrane was compared in normotensive Wistar-Kyoto (WKY), spontaneously hypertensive (SHR), and stroke-prone SHR (SHR-SP) rats. This was performed on isolated ghost membranes by measuring the incorporation of 32P from [ gamma-32P ] adenosine triphosphate (ATP) into the diphosphoinositides (DPI) and the triphosphoinositides (TPI) which were the only 32P-labeled phospholipids. 32P-labeling of TPI was altered in adult and 3-week-old SHR as well as in SHR-SP compared to WKY controls; the radioactivity associated with TPI in hypertensive rats was about 30% lower than that associated with TPI in age-matched normotensive controls. By contrast, the radioactivity associated with DPI was similar in both hypertensive and normotensive rats. Measurement of the phosphoinositide distribution in both SHR and WKY indicates that the change observed in 32P-TPI could not be accounted for by a reduced phosphatidylinositol content in SHR membrane. Measurement of the Mg2+-activated TPI-phosphomonoesterase and of the Ca2+-activated polyphosphoinositide phosphodiesterase activities did not show any significant difference between SHR and WKY. It thus appears that the altered phosphoinositide metabolism observed in hypertensive rats was a consequence of some alteration in the activity of kinases which are responsible for the conversion of phosphatidylinositol into DPI and TPI. These results also suggest that the defect in phosphoinositide metabolism observed in genetically hypertensive rats was not a consequence of the blood pressure elevation and could be related to the pathogenesis of hypertension.
Effects of intrarenal infusion of calcium entry blockers in anesthetized dogs.
Authors: Dietz J R , Davis J O , Freeman R H , Villarreal D , Echtenkamp S F
Published: June 2012

Renal function and renin release were studied in anesthetized, uninephrectomized dogs during intrarenal infusions of the calcium influx blockers, verapamil and nifedipine. Verapamil increased renal blood flow by 20% (p less than 0.05) but did not alter glomerular filtration rate. Verapamil produced five-to-seven fold increases in urine flow and the rates of excretion of sodium and chloride (p less than 0.01). Significant increases in the rates of excretion of potassium, calcium and magnesium were also observed. Despite its striking effects on renal function, verapamil, in nonhypotensive doses, failed to alter renin secretion. Intrarenal infusion of nifedipine had no consistent effect on renal blood flow or the rate of glomerular filtration but increased urine flow and the rates of excretion of sodium and chloride by more than three fold (p less than 0.01). Nonhypotensive doses of nifedipine had no significant effect on renin release. In dogs with a denervated nonfiltering kidney, an intrarenal verapamil or nifedipine infusion did not produce a significant change in renin release. This study demonstrates a striking effect of calcium entry blockers on the reabsorption of sodium, chloride, and water by the renal tubules in intact dogs but renin release did not increase unless hypotension occurred.
Lithium-sodium countertransport in erythrocytes of normal and hypertensive subjects. Relationship with age and plasma renin activity.
Authors: Brugnara C , Corrocher R , Foroni L , Steinmayr M , Bonfanti F , De Sandre G
Published: June 2012

Lii-Nao countertransport was measured in red blood cells of 58 normotensive subjects (27 females and 31 males), 60 patients with essential hypertension (26 females and 34 males), and in 28 with secondary hypertension (19 females and 9 males). The mean values (+/- SEM) expressed as mmol Li (1 red cells X hr)-1 were 0.18 +/- 0.02 (females) and 0.20 +/- 0.01 (males) in the control group, 0.34 +/- 0.04 (females) and 0.39 +/- 0.03 (males) in essential hypertension, 0.16 +/- 0.03 (females) and 0.19 +/- 0.02 (males) in secondary hypertension. The mean value of Lii-Nao countertransport obtained in essential hypertension was statistically different from those obtained in both normals (p less than 0.001) and patients with secondary hypertension (p less than 0.001). A negative correlation was found between age and Lii-Nao countertransport in normotensive males (r = - 0.648; p less than 0.001) but neither in normal females nor in patients with essential hypertension. A positive correlation (r = + 0.425; p less than 0.05) was found between plasma renin activity after intravenous furosemide and Lii-Nao countertransport in essential hypertension. These findings support the hypothesis of a characteristic cation transport across the red blood cell membrane of patient with essential hypertension which might be correlated with the plasma renin activity.
Studies of the mechanisms underlying impairment of beta-adrenoceptor-mediated effects in human hypertension.
Authors: Trimarco B , Volpe M , Ricciardelli B , Picotti G B , Galva M D , Petracca R , Condorelli M
Published: June 2012

To investigate the impairment of beta-adrenoceptor responsiveness in human hypertension, we evaluated the effect of an oral salt load (400 mEq/day of NaCl for 7 days) on plasma catecholamine concentrations and beta-adrenoceptor-mediated effects in 11 young patients with mild essential hypertension. Responses of heart rate and plasma cAMP to isoproterenol administration were used as indices of beta-adrenoceptor responsiveness. Salt loading induced a significant reduction in the dose of isoproterenol required to raise the heart rate by 25 bpm (CD25) (from 7.6 +/- 1.5 to 5.3 +/- 0.9 micrograms, p less than 0.05) and an increase in the slopes of the regression lines for heart rate changes and isoproterenol doses (delta HR/IS) (from 3.3 +/- 0.6 to 4.7 +/- 0.7, p less than 0.05) and for plasma cyclic AMP (cAMP) level changes and isoproterenol doses (delta cAMP/IS) (from 0.3 +/- 0.06 to 1.4 +/- 0.3, p less than 0.05). After salt loading there was a significant reduction in plasma catecholamine concentrations with a significant relationship between changes in upright plasma epinephrine levels and changes in CD25 (r = 0.904, p less than 0.01) and in the slopes for delta HR/IS (r = 0.983, p less than 0.001) and delta cAMP/IS (r = 0.922, p less than 0.001). These results support the hypothesis that the impairment of beta-adrenoceptor sensitivity observed in human hypertension is associated with a beta-adrenoceptor overstimulation due to chronically elevated adrenergic tone.
Permeability of intestinal microvessels in chronic arterial hypertension.
Authors: Laine G A , Granger H J
Published: June 2012

We studied changes in intestinal microvascular permeability resulting from chronic arterial hypertension. Normotensive dogs and dogs made chronically hypertensive utilizing the one-kidney, one clip Goldblatt technique were used to obtain values for: arterial pressure, portal pressure, intestinal lymph flow, and the lymph-to-plasma protein concentration ratio (CL/Cp). Values for the normotensive dogs were 111 mm Hg, 7.1 mm Hg, 6.2 ml/hr, and 0.64, respectively, while values for the chronically hypertensive dogs were 165 mm Hg, 7.3 mm Hg, 12.5 ml/hr, and 0.66, respectively. Control lymph flow in the hypertensives was 100% greater than in the normotensives, while there was no significant difference in control CL/Cp between the two groups. When portal venous pressure was acutely increased to 30 mm Hg, lymph flow increased to approximately the same maximum value in both groups. This represents an eightfold increase in normotensive and a fourfold increase in hypertensive lymph flows. The reflection coefficient determined as 1 - (CL/Cp) for total proteins at maximum lymph flow was 0.78 for the normotensives and 0.56 for the hypertensives. An electrophoretic analysis indicated sieving of large molecular weight protein fractions was considerably reduced in the hypertensives when compared to the normotensives. Our results indicate a significant increase in intestinal microvascular permeability to macromolecules resulting from the one-kidney, one clip Goldblatt model of chronic arterial hypertension.
Blood pressure response to dietary sodium restriction in normotensive adults.
Authors: Miller J Z , Daugherty S A , Weinberger M H , Grim C E , Christian J C , Lang C L
Published: June 2012

Sixteen healthy, normotensive husband-wife pairs participated in a study to investigate the effect of reduction of dietary sodium intake (goal less than or equal to 60 mEq/day) on blood pressure. Sodium excretion decreased from a control average of 152.7 +/- 10.1 (SE) mEq/day to 69.5 +/- 4.5 mEq/day (p less than 0.001). Results indicated significant decreases in both systolic (p less than 0.001) and diastolic (p less than 0.001) blood pressure after a period of sodium restriction. In the entire group, there was no significant change in potassium excretion (58.4 +/- 3.2 vs 54.6 +/- 3.5 mEq/day) or body weight (76.0 +/- 2.8 vs 75.3 +/- 2.7 kg). Although there was variability in the blood pressure response, the decrease in blood pressure was significantly correlated with the magnitude of sodium restriction (r = 0.36, p less than 0.03). These results indicate that the blood pressure response to sodium restriction may not be limited to individuals with hypertension and that the response is heterogeneous in normotensive subjects.
Responses of the stenosed and contralateral kidneys to [Sar1, Thr8] AII in human renovascular hypertension.
Authors: Textor S C , Novick A , Mujais S K , Ross R , Bravo E L , Fouad F M , Tarazi R C
Published: June 2012

To better define the intrarenal hemodynamic effects of angiotensin in human renovascular hypertension, 10 patients underwent renal hemodynamic and functional measurements before and during infusion of a competitive angiotensin analog, [Sar1, Thr8] AII. Eight had technically satisfactory split function studies. Despite a fall in mean arterial pressure (132 +/- 6 to 121 +/- 6 mm Hg, p less than 0.05) and humoral changes consistent with angiotensin-mediated hypertension, the intrarenal effects of this analog were commonly those of an angiotensin agonist, producing vasoconstriction and sodium retention. This was quantitatively greatest in the contralateral kidney, whose preinfusion sodium excretion (86 +/- 30 microEq/min vs 25 +/- 9 microEq/min, p less than 0.02) and glomerular filtration rate (76 +/- 7 ml/min vs 41 +/- 7 ml/min, p less than 0.01) were higher than the stenotic kidney. In some cases, an increase in renal blood flow and rise in sodium excretion were evident during angiotensin blockade, suggesting a tonic intrarenal action of angiotensin. Although renin vein renin values differed markedly between the stenotic and contralateral kidney (ratio = 2.05 +/- 0.30), relative changes in effective renal plasma flow were correlated (r = 0.84: p less than 0.01) during infusion of this analog. These results underscore the differences in sensitivities between vascular beds to the effects of angiotensin II and the major role of the contralateral kidney in renal function and sodium homeostasis in human renovascular hypertension.
Role of endothelium in dilator responses of spontaneously hypertensive rat arteries.
Authors: Konishi M , Su C
Published: June 2012

The possible role of endothelium in the vascular responses to vasodilator drugs was studied in relation to experimental hypertension. Short ring segments of the thoracic aorta and femoral artery were removed from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. They were rubbed on the intimal surface to destruct endothelial cells or unrubbed, and bathed in Krebs-bicarbonate solution for isometric recording of contractile and relaxant responses. The relaxant response to acetylcholine was abolished by rubbing all arteries tested. Rubbing also significantly attenuated the relaxation induced by adenosine in the SHR aorta and SHR and WKY femoral artery, and attenuated the relaxation by isoproterenol in the SHR femoral artery. In contrast, contractile response to norepinephrine was augmented by intimal surface rubbing in all arteries except the aorta of WKY. It is suggested that an endothelial compensatory mechanism develops to offset the diminished relaxant and/or increased contractile responsiveness of smooth muscle cells in the hypertensive rat arteries.
Role of catecholamines and vasopressin in cardiovascular responses to bilateral dorsolateral transection of the medulla oblongata in the rat.
Authors: Zukowska-Grojec Z , Bayorh M A , Zerbe R L , Palkovits M , Kopin I J
Published: June 2012

The role of sympathetic and other pressor systems in the development of fulminant hypertension induced by baroreceptor deafferentation is still unclear. We studied the effects of acute hypertension produced by bilateral dorsomedullary knife cuts lateral to the nucleus tractus solitarii (DMK-cut) on plasma norepinephrine (NE), epinephrine (E), and vasopressin (VP) in conscious, tail-artery-cannulated rats. In saline-pretreated (SAL) rats, DMK-cut caused a significant (p less than 0.001) rise in mean blood pressure (MAP, +68 +/- 3 mm Hg), heart rate (HR, +97 +/- 19 bpm), NE (+2.5 +/- 0.3 ng/ml), E (+2.7 +/- 0.4 ng/ml), and VP (+115 +/- 34 pg/ml) compared to sham-operated rats. Neither sympathetic blockade with chlorisondamine (CHLO, 10 mg/kg, s.c.) nor elimination of the pressor effects of VP by use of Brattleboro rats or the VP pressor antagonist resulted in a maximal MAP response significantly different from that in the SAL + DMK-cut group. However, CHLO-pretreatment of Brattleboro rats completely abolished the increase in MAP and HR. It is suggested that the bilateral DMK-cut causes acute hypertension, probably due to the abolition of baroreceptor reflexes by central interruption of neural connections of the nucleus tractus solitarii. It appears that both the increased sympathoadrenomedullary activity and VP release normally contribute to this hypertension; however, either one is sufficient to sustain the elevated blood pressure.
Temperature dependence and bidirectional cation fluxes in red blood cells from spontaneously hypertensive rats.
Authors: Harris A L , Guthe C C , van't Veer F , Bohr D F
Published: June 2012

The net passive influx of Na+ and efflux of K+ (orthodirection) through the red blood cell membranes from spontaneously hypertensive rats (SHR) were observed to be significantly higher (p less than 0.05) than those of three strains of normotensive rats when the measurements were made at 4 degrees C. Similar comparative studies, carried out at 37 degrees C, in the absence or presence of ouabain, showed no difference in these fluxes through this membrane from SHR compared to those from Wistar-Kyoto (WKY) rats, one of the normotensive strains. A study was undertaken to determine the temperature at which the greater cation fluxes in SHR red blood cells occurred. The net fluxes of Na+ and K+ decreased as the temperature was reduced from 37 degrees to 15 degrees C, but a paradoxical increase in the fluxes was observed as the temperature was decreased from 15 degrees to 4 degrees C. Only with this temperature shift (15 degrees to 4 degrees C) was the increase in flux significantly greater in SHR than in WKY cells. Subsequent studies were designed to determine whether the difference in the transport systems of red blood cells of SHR and WKY could be observed in fluxes of these cations in either direction across the membrane. For "reverse direction" flux studies, red blood cells were loaded with Na+ (to 130 mEq/liter cell water) and depleted of K+ (to 30 mEq/liter cell water) by incubation with the ionophore monensin.(ABSTRACT TRUNCATED AT 250 WORDS)
Increased levels of new spasmogenic substances released by trypsin from plasma of hypertensive rats.
Authors: Reis M L , de Jesus W D , Bertramini-Sabbag L M , Krieger E M , Greene L J
Published: June 2012

The present study was undertaken to evaluate the participation of the kallikrein-kinin system in the normalization of blood pressure after release of the clip in one-kidney, one clip hypertensive rats ( 1K1C ). Kininogen was determined before and after unclipping by tryptic digestion of denatured rat plasma, and spasmogenic activity was measured with isolated guinea pig ileum. In contrast to human plasma for which bradykinin (BK) is the only trypsin-releasable spasmogenic substance ( TRSS ), rat plasma contains non-BK TRSS (Fractions P1 and P2) as well as BK. Fractions P1 and P2 were separated from BK by SP-Sephadex chromatography. An increase of total TRSS was demonstrated 60 days after clipping and reached a maximum at approximately Day 75, which was two times that of the normotensive controls (NC). The level of total TRSS did not change after unclipping . The increased level of TRSS in the hypertensive state confirmed the observations of other investigators who reported increased kininogen levels but who could not distinguish between BK and non-BK TRSS because bioassays were performed without prior chromatographic separation of the spasmogenic activities. Fractions P1 and P2 were present in the TRSS of both 1K1C and NC plasma, but were two to six times higher in 1K1C and thus probably accounted quantitatively for the increased TRSS in 1K1C . The data suggest that in the hypertensive state there is an alteration in the relative amounts of some plasma proteins that contain non-BK TRSS within their amino acid sequences. Fractions P1 and P2 also contain potentiating peptides and have not yet been purified to homogeneity.(ABSTRACT TRUNCATED AT 250 WORDS)
Noradrenergic transmission in the isolated portal vein of the spontaneously hypertensive rat.
Authors: Westfall T C , Meldrum M J , Badino L , Earnhardt J T
Published: June 2012

The effect of electrical field stimulation (1, 2, 5, 10 Hz for a total of 480 pulses at 15-minute intervals) on the release of 3H-norepinephrine from the superfused portal vein of spontaneously hypertensive rats (SHR) or Wistar-Kyoto rats (WKY) of various ages was studied. The ages of the animals were (in weeks) 5-6 (prehypertensive), 8-10 (young hypertensives), 16-18 (older hypertensives), and 28 (mature hypertensives). There was no difference in the release of 3H-norepinephrine or developed tension of the portal vein to any frequency of field stimulation of SHR or WKY at 5-6 weeks of age. However, there was a significantly greater release of 3H-norepinephrine and developed tension of veins of SHR in response to low (1 or 2 Hz) but not high frequencies (5 or 10 Hz) at 8-10, 16-18, and 28 weeks of age. Vessels from hypertensive animals also developed greater resting tension and spontaneous activity, which was reduced to that of WKY in the presence of an alpha-adrenergic antagonist. The alpha 2 selective adrenergic antagonist yohimbine produced the same degree of enhancement of release of 3H-norepinephrine to field stimulation of veins obtained from both SHR and WKY at 5-6, 8-10 and 16-18 weeks of age. However, the facilitory effect of yohimbine was significantly attenuated in portal veins obtained from SHR at 28 weeks of age compared to age-matched WKY.(ABSTRACT TRUNCATED AT 250 WORDS)
Cold pressor test as a predictor of hypertension.
Authors: Wood D L , Sheps S G , Elveback L R , Schirger A
Published: June 2012

To determine the usefulness of the cold pressor test as a predictor of hypertension, we compared the blood pressure recordings available from 142 patients in 1979 with readings obtained during performance of two cold pressor tests, the first in 1934 when these subjects were children, and the second in 1961. Forty-eight subjects were hyperreactors to the tests in either 1934 or 1961, and 94 were normoreactors. At last follow-up, blood pressures in 14 of the hyperreactors were between 140 and 160 mm Hg systolic or 90 and 100 mm Hg diastolic (Stratum 1) and in 20 exceeded 160 mm Hg systolic or 100 mm Hg diastolic (Stratum 2). Ten normoreactors had casual blood pressures in Stratum 1 and eight in Stratum 2. Hypertension had thus occurred in 71% of the hyperreactors and 19% of the normoreactors. Fifteen hyperreactors were receiving antihypertensive therapy, and this reduced the severity of the casual blood pressure elevation in most patients to Stratum 1. Antihypertensive therapy had been started in three normoreactors. The duration of follow-up, 45 years, and the mean age at follow-up, almost 57 years, were greater in this study than in any previously reported study. Early hyperreactivity was related to future hypertension in enough subjects to suggest that an abnormal response to an external cold stimulus may be useful as an indicator of future hypertension.
Interaction of internal Na+ and external K+ with the erythrocyte Na+, K+ cotransport system in essential hypertension.
Authors: Price M , Hannaert P , Dagher G , Garay R P
Published: June 2012

External K+ inhibits the maximal rate of outward Na+, K+ cotransport in human red cells with no effect on the apparent affinity for internal Na+. The K+ concentration giving half-maximal inhibition (KIK) varied from 16 to 30 mM in 24 normotensive control subjects. Six of the 38 hypertensive patients showed a KIK above the upper limit of this normal range. Only three hypertensive patients showed a KIK below normal range. The internal Na+ content giving half-maximal stimulation of outward Na+, K+ cotransport (KSNa) was measured in the hypertensive patients (a normal range of KSNa = 9 to 16 mmol/liter cells was previously established in 50 normotensive control subjects). Eighteen hypertensive patients showed an abnormally high KSNa, as previously described in hypertensive patients whose Na+, K+ cotransport system had a low affinity for internal Na+ (Co -). Comparison of KSNa with KIK showed that all six hypertensive patients with high KIK and all three hypertensive patients with low KIK were Co - hypertensive.
Effects of sodium depletion on inactive and active renin from dog kidney and plasma.
Authors: Kawamura M , Akabane S , Ito K , Ikeda M
Published: June 2012

The relationship of active renin and inactive renin (trypsin-activated angiotensin-I-forming enzyme) to sodium depletion was examined in renal and peripheral plasma and at the subcellular level in the kidneys of dogs. Subcellular fractionation was carried out by discontinuous sucrose density (1.5 and 1.6 M) centrifugation. Sodium depletion selectively caused a six- to sevenfold increase in the renal content of inactive and active renins in the original homogenate, while the subcellular distribution patterns of these enzymes were little changed. Of the total granule fractions of 1.5 M sucrose (F1), 1.6 M sucrose (F2), and sediment (F3), approximately 80% of inactive renin was recovered in F1, which was rich in microsomes, while about 50% of active renin was in F2. The ratio of inactive to active renin was 0.02 in F1 and 0.003 to 0.004 in F2. Sodium depletion also caused a 20-fold increase in active renin and a twofold increase in inactive renin in peripheral plasma. The renal venous-arterial concentration difference of inactive renin was statistically significant in low-sodium dogs, although it was not significant in controls. The ratio of inactive to active renin was 0.2 to 0.4 in plasma from low-sodium dogs, while it was 1.5 to 3 in plasma from control dogs. These results suggest that plasma inactive renin originates, at least in part, in the kidney.
Cardiovascular hemodynamics and vasopressin blockade in DOCA-salt hypertensive rats.
Authors: Yamamoto J , Yamane Y , Umeda Y , Yoshioka T , Nakai M , Ikeda M
Published: June 2012

In conscious rats with near-malignant phases of DOCA-salt (DS) hypertension, hemodynamics were studied with microspheres before and after administration of a vasopressin (VP) vasopressor antagonist in relation to plasma VP levels (pVP). Compared to the controls, the DS rats showed significant elevations in mean arterial pressure (MAP), total vascular resistance (TVR), and pVP, and a flow redistribution from kidney and spleen to skeletal muscles and heart, with increased vascular resistance in almost all organs. The antagonist elicited no significant systemic hemodynamic effects in DS rats as a whole; however, two subgroups, responders vs nonresponders, were identified according to the effects on MAP. In responders with a pVP of 29.2 +/- 2.7 (SE) pg/ml, the antagonist lowered MAP (-24.9 +/- 5.9 mm Hg) and TVR significantly, while in nonresponders with a pVP of 15.2 +/- 3.4 pg/ml, there were no effects. The major antagonist-induced regional responses were increased flow and decreased vascular resistance in skeletal muscles and skin in whole DS rats, and additionally in the gastrointestinal tract, portal organs, and testes in the responders. Significant correlations were observed between pVP, MAP, TVR, and depressor responses to the antagonist only when all data for DS and control rats were pooled. Thus, the systemic hemodynamic effects of VP are important only in responders with exceedingly elevated pVP. VP contributes significantly to the regional hemodynamic abnormalities in skeletal muscles and skin in whole DS rats, and also in several other organs in the responders.
Temperature dependence of ionic transport and norepinephrine stimulation of rat aorta during DOCA hypertension.
Authors: Warden D H , Jones A W
Published: June 2012

Temperature perturbation was used to determine whether increased turnover of Na, K, and Cl at 37 degrees C in aortas from rats made hypertensive with deoxycorticosterone acetate salt treatment (DOCH) reflects an increased number of transport sites that individually maintain relatively normal function. Decreasing temperature reduced the resting effluxes of 42K, 36Cl, and 24Na (active and passive) from control and DOCH in parallel fashion. The slope of the Arrhenius plots (activation energies) and the transition temperatures at which major changes in slope occurred were similar in controls and DOCH. In contrast to the results for resting effluxes, the temperature dependence for the effects of norepinephrine (NE) on contraction and on 42K and 36Cl effluxes in DOCH differed from controls. At 20 degrees C, the responses to NE were either abolished or greatly suppressed in DOCH, as compared to controls, while no significant differences between the two groups were observed at 30 degrees C. These results indicate that alterations in resting 42K, 36Cl, and 24Na effluxes in DOCH may result from an increased number of transport sites in the membranes of vascular smooth muscle. The concept that alterations occurred in the integral components of the membrane is also supported by the observation that increased resting 42K and 36Cl effluxes in DOCH at 37 degrees C persisted in aortas that had undergone cold storage for 2 days before incubation at 37 degrees C. The altered temperature dependence for the effects of NE on DOCH, compared to controls, indicates that the involvement of agonist-receptor-membrane events may be dissociated from the alterations in resting ionic fluxes.
Connective tissue accumulation in the left coronary artery of young SHR.
Authors: Anversa P , Melissari M , Tardini A , Olivetti G
Published: June 2012

The left coronary artery of 21-, 28-, and 45-day-old spontaneously hypertensive rats and Wistar-Kyoto rats was analyzed morphometrically to evaluate the structural alterations of the vessel wall during the development of genetically determined hypertension. In 45-day-old rats, hypertension was associated with a significant expansion of the partial volume of collagen and ground substance (119%) within the arterial wall. This change exceeded the concurrent accumulation of elastin (77%) and smooth muscle cell mass (34%). The growth of the muscle compartment was also characterized by a marked increment of rough endoplasmic reticulum (103%). The increase in the mural concentration of fibrous proteins at this early age may be viewed as the initial adverse effect of hypertension on muscular arteries.
Neural and local control of arterioles in SHR.
Authors: Lombard J H , Hess M E , Stekiel W J
Published: June 2012

This study sought to determine if neural influences and/or alterations in arteriolar responses to oxygen could contribute to an elevated microvascular resistance in spontaneously hypertensive rats (SHR). Diameters of third-order arterioles (3A) and fourth-order arterioles (4A) were measured in the cremaster muscle of 12- to 15-week-old SHR and normotensive Wistar-Kyoto (WKY) controls anesthetized with pentobarbital. The preparation was suffused with physiological salt solution (PSS) equilibrated with various concentrations of oxygen (0% O2, 5% O2, or 10% O2) with and without local neural blockade with 10(-7) g/ml tetrodotoxin (TTX). Total active tone was assessed with 10(-4) M adenosine. SHR 3A (but not 4A) exhibited a smaller resting diameter than WKY, and larger dilations in response to TTX and adenosine. When suffusion solution PO2 was elevated in the presence or absence of TTX, SHR arterioles constricted more than did those of WKY, and SHR 4A exhibited a higher incidence of complete closure. Therefore, both neural influences and local vascular control mechanisms may contribute to an elevated microvascular resistance in SHR.
Role of the renal nerves in one-kidney, one clip hypertension in rats.
Authors: Norman R A , Murphy W R , Dzielak D J , Khraibi A A , Carroll R G
Published: June 2012

The effects of renal denervation on the onset and maintenance of one-kidney, one clip Goldblatt (1K1C) hypertension were determined. Renal denervation was performed at the time of 1K1C surgery, and was repeated at 3-week intervals to prevent renal nerve regeneration. Denervation delayed the onset of 1K1C hypertension by about 5 weeks, but the final hypertensive state was unaltered. Mean arterial pressure (MAP) averaged 196 +/- 11.4 mm Hg in six rats at 9 weeks after 1K1C surgery and 194 +/- 11.3 mm Hg in eight renal-denervated rats at this time. The delay in the development of 1K1C hypertension following renal denervation could not be explained by interference with renin release. This delay in the development of hypertension could be prevented, however, in renal-denervated 1K1C rats by substituting saline for the drinking water. Two weeks after 1K1C surgery and a high sodium diet, MAP averaged 164 +/- 6.4 mm Hg in eight rats rats with intact renal nerves and 173 +/- 4.8 mm Hg in nine renal-denervated rats. Intact renal nerves are not necessary for the development or maintenance of 1K1C hypertension. Renal denervation delays development of 1K1C hypertension, possibly by delaying the ability of these rats to retain sodium.
Attenuated arteriolar dilator responses to calcium in genetically hypertensive rats.
Authors: Overbeck H W
Published: June 2012

Vascular responses to calcium were studied in 14 genetically hypertensive (GH) rats of the New Zealand strain and 16 weight- and age-matched normotensive parent strain control rats under chloralose-pentobarbital anesthesia. Calcium (chloride or gluconate) in an isosmolar solution was infused intraarterially into the hindlimb vascular bed which was vascularly isolated, innervated, and pump-perfused (blood, 1 ml/min). Increases in limb plasma calcium concentrations up to 30 mEq/liter decreased limb vascular resistance, with no evidence for vasoconstriction. In GH rats decreases in limb vascular resistance in response to increments in limb plasma calcium concentrations of 3.6 to 10.8 mEq/liter were significantly (p less than 0.02) attenuated compared to age-matched controls. When responses in GH were compared to weight-matched controls, similar trends toward attenuation reached significance (p less than 0.02) at Ca2+ increments of 10.8 mEq/liter. In eight other GH rats, we measured total serum calcium concentrations and found them reduced (4.94 +/- 0.08 mEq/liter), especially as compared to values in eight rats of an unrelated Wistar strain (5.42 +/- 0.04 mEq/liter; p less than 0.05). These experiments provide evidence that, over physiological ranges, calcium relaxes arteriolar smooth muscle in rats and that this vasodilation is attenuated in genetically hypertensive rats. Thus, both the lower serum levels of calcium and the attenuated responses to calcium may contribute to the elevated peripheral vascular resistance and hypertension in these rats.
Influence of captopril and enalapril on regional vascular alpha-adrenergic receptor reactivity in SHR.
Authors: Richer C , Doussau M P , Giudicelli J F
Published: June 2012

The effects of short-term oral treatment with captopril and enalapril (two angiotensin-I-converting-enzyme inhibitors [ACEIs] that were administered in equipotent antihypertensive doses) on the systemic vasopressor response and on the renal, mesenteric, and hindlimb vascular responses to cirazoline and UK-14,304 (alpha 1- and alpha 2-adrenergic receptor-specific agonists, respectively) were investigated in adult pithed spontaneously hypertensive rats (SHR) of the Okamoto-Aoki strain. In the nonbinephrectomized animal, captopril and enalapril reduced to the same extent the systemic blood pressure and renal and hindlimb vascular resistances. They also decreased to the same extent systemic pressor and regional vasoconstrictor responses to cirazoline and UK-14,304, especially in the renal and mesenteric vascular beds. Simultaneously, the effects of angiotensin I and angiotensin II on the pressor response were abolished and almost not modified. In the binephrectomized animals, captopril and enalapril no longer reduced the systemic blood pressure and regional vascular resistances, but whereas the sympathoinhibitory effect of captopril vs the systemic pressor and regional vasoconstrictor responses to cirazoline and UK-14,304 persisted, those of enalapril disappeared.(ABSTRACT TRUNCATED AT 250 WORDS)
Vascular angiotensin II receptors in SHR.
Authors: Schiffrin E L , Thomé F S , Genest J
Published: June 2012

We investigated the density (Bmax) of angiotensin II (ANG II) receptors in the mesenteric vascular bed of spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto (WKY) control rats. In 12-week-old SHR, the Bmax and the dissociation constant (Kd) of ANG II binding sites were not different from those of WKY rats in the sodium replete state or after sodium depletion. In prehypertensive (4- and 6-week-old) SHR, the Bmax of the vascular ANG II receptors was significantly higher (p less than 0.05) than in age-matched WKY rats. This result could not be attributed entirely to differences in the circulating renin-angiotensin-aldosterone system in 4-week-old-rats. In 6-week-old WKY rats, the plasma renin activity was significantly higher (p less than 0.05), which may account in part for the higher density of ANG II binding sites in SHR. There was an age-related decrease in the number of ANG II receptors in SHR. The increased density of vascular ANG II receptors in young SHR may play a role in the development of high blood pressure in this model of spontaneous hypertension. The higher number of ANG II binding sites in young SHR is not selective for ANG II receptors, since an increased density of alpha 1-adrenergic receptors was also found in the mesenteric arteries of 4-week-old SHR.
Blood pressure, lanthanum-, and norepinephrine-induced mechanical response in thoracic aortic tissue.
Authors: Laher I , Triggle C
Published: June 2012

The responses of isolated thoracic aortic rings to 10(-5) M norepinephrine (NE) and 5 mM lanthanum chloride (La3+) were compared in tissues from 6- to 8-week-old and 12- to 16-week-old rats. Twelve strains of rats were selected: spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), genetically related outcross F1 and F2, backcross BC1(S) and BC1(W), and Wistar, SHR/Wistar, and Wistar/WKY crosses, Sprague-Dawley (SD), and also Dahl salt-sensitive (DS) and salt-resistant (DR) rats. The La3+ response, expressed as the percentage of the maximal response to NE, demonstrated both age and blood pressure (BP) components in the SHR, WKY, F1, F2, and BC rats; however, when the La3+ response was expressed as mg force/mg tissue, no significant differences within these same groups were noted. The magnitude of the NE response in the same group of rats was inversely related to the BP of the 12- to 16-week-old animals (r = -0.45), and was not affected by treatment of the animal from conception with alpha-methyldopa. Aortic tissues from DS, but not DR or SD rats, demonstrated a response to La3+ which increased with the BP of the rat. This was not observed in prehypertensive DS rats and was prevented by the control of hypertension with either hydrochlorothiazide or MK-421 (a converting-enzyme inhibitor). We conclude that the reduced NE response in aortic tissues from SHR and related hypertensive rats reflects an inherent defect in the vascular smooth cell of the rat and is unaffected by BP control with antihypertensive drug therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Red cell cotransport activity and sodium content in black men. Relationship to essential hypertension.
Authors: Ringel R E , Hamlyn J M , Schaeffer J , Hamilton B P , Kowarski A A , Blaustein M P , Berman M A
Published: June 2012

Furosemide-sensitive sodium and potassium cotransport and intracellular sodium content ([Na]i) were measured in erythrocytes (red blood cells, RBCs) from a population of 90 adult black men with and without essential hypertension (EH). The mean values for sodium cotransport activity, expressed as furosemide-sensitive Na efflux (mmol/liter RBC/hr), were not significantly different among the EH patients and two control groups, normotensive subjects with a positive history (N+) and those with a negative family history (N-) for hypertensive disease (EH: 154 +/- 123, n = 53; N+: 167 +/- 93, n = 12; and N-: 207 +/- 142, n = 20; all values are means +/- SD). The mean [Na]i 9.66 +/- 3.02 mmol/liter RBC (n = 56) for the EH group was greater than the mean value for the N- control group (7.96 +/- 1.97, n = 20; p less than 0.05). The N+ group also displayed a higher mean [Na]i (10.38 +/- 3.18, n = 12; N+ vs N- p less than 0.01). Although there was substantial overlapping of [Na]i values between the groups and no clear dividing line, the distribution curve of the [Na]i values in EH was skewed toward higher concentrations than in N-. Nevertheless, we must conclude that erythrocyte cotransport and [Na]i are not clinically useful in the identification of EH in black men.
Blood pressure and hormonal responses to aerobic exercise.
Authors: Kiyonaga A , Arakawa K , Tanaka H , Shindo M
Published: June 2012

Twelve patients with essential hypertension (WHO stages I-II) were subjected to mild aerobic exercise for 10 to 20 weeks. The time course of changes in the resting blood pressure and multiple hormonal responses (plasma catecholamines, prostaglandin E, renin-angiotensin system, kallikrein-bradykinin system) were monitored. Depressor response of both systolic and diastolic pressures was seen, and after 5 weeks of exercise blood pressure stabilized at a significantly lower level. Adjustment of work load in response to increased physical fitness at the 10th week produced further reduction of blood pressure especially in diastole. After exercise therapy we found significant reductions in plasma catecholamine levels, and increases in levels of plasma prostaglandin E and the urinary excretion of sodium. A reduction in systolic/diastolic (mean) pressures by more than 20/10 (13) mm Hg was seen in 50% of patients after 10 weeks and in 78% after 20 weeks of exercise. Those who achieved effective blood pressure fall after 10 weeks of training (n = 6) were compared with the rest (n = 6). This analysis revealed that the initial value of plasma renin activity of the former was significantly lower than that of the latter. Significant negative correlations (r = -0.78) also were observed between the blood pressure reduction and corresponding initial value of plasma renin activity. These results indicate that exercise therapy is a potent nonpharmacological tool for the treatment of essential hypertension, especially of the low renin type. Both diminished sympathoadrenergic activity and enhancement of prostaglandin mechanisms might be responsible for the falls in arterial pressure.
Epinephrine enhances neurogenic vasoconstriction in the rat perfused kidney.
Authors: Quinn P , Borkowski K R , Collis M G
Published: June 2012

Epinephrine has been implicated in the genesis of some forms of hypertension. We have investigated the effects of epinephrine on vasoconstrictor responses evoked by adrenergic stimuli in the isolated perfused rat kidney. Low concentrations of epinephrine (2.5 - 5 X 10(-9) M) increased the amplitude of vasoconstrictor responses evoked by electrical stimulation of the renal adrenergic nerves. These concentrations of epinephrine had no effect on the basal perfusion pressure of the kidney or on the amplitude of vasoconstrictor responses evoked by exogenous norepinephrine. The potentiating effect of epinephrine persisted after infusion of the amine had ceased. Kidneys that had been perfused with 3H-epinephrine accumulated radioactivity, which could then be released by renal nerve stimulation. Cocaine (3 X 10(-5) M) reduced the renal accumulation of 3H-epinephrine and abolished both the persistent potentiating effect of the amine and the release of radioactivity evoked by subsequent nerve stimulation. The potentiating effect of epinephrine infusion was abolished by the beta 2-selective adrenergic receptor antagonist ICI 118,551 (3 X 10(-8) M), but not by the beta 1-selective adrenergic receptor antagonist atenolol (10(-6) M). These results indicate that concentrations of epinephrine that can be achieved during acute stress can enhance the amplitude of neurogenic vasoconstrictor responses. This effect appears to be mediated via a prejunctional beta 2-adrenergic receptor. The persistent nature of this effect may be due to the neuronal accumulation and subsequent release of epinephrine.
Cerebrospinal fluid angiotensin II immunoreactivity is not derived from the plasma.
Authors: Mikami H , Suzuki H , Smeby R R , Ferrario C M
Published: June 2012

To elucidate whether the presence of angiotensin II immunoreactivity (ANG II-ir) in the cerebrospinal fluid (CSF) of the dog is in part due to passage of the peptide across the CSF-blood-brain barrier, [Ile5] angiotensin II (ANG II) was infused intravenously for 7 days in conscious, trained dogs at a rate of 10 micrograms/kg/day. Mean arterial pressure (MAP) and heart rate were monitored each day, and samples of arterial blood and CSF (with a catheter secured into the cisterna magna) were drawn at regular intervals for determination of catecholamine levels, ANG II-ir, and electrolyte levels. Within 2 days after ANG II infusion, MAP stabilized at 35 +/- 1 mm Hg (mean +/- SE, p less than 0.001) above control values. The hypertension was associated with bradycardia, suppressed plasma renin activity, and a fall in both plasma and CSF Na+ concentrations. These changes coincided with a considerable and sustained decrease in the levels of plasma and CSF norepinephrine. On the other hand, levels of epinephrine and K+ in the two compartments remained unchanged. Although concentration of ANG II-ir in plasma was augmented markedly (368% above control values, p less than 0.001), ANG II-ir in the CSF remained within the low values measured in the control period.(ABSTRACT TRUNCATED AT 250 WORDS)
A new mechanism in one-kidney, one clip hypertension.
Authors: Skeggs L T , Dorer F E , Lentz K E , Kahn J R , Emancipator S N
Published: June 2012

The renin-angiotensin system does not appear to be involved in the maintenance of elevated blood pressure in experimental one-kidney, one clip hypertension. Paradoxically, direct immunization with purified hog kidney renin lowers the blood pressure of rabbits with this form of hypertension. Antirenin antibodies were removed and the IgG fraction prepared from the plasma of such immunized rabbits. The antibodies thus obtained lowered the blood pressure of other hypertensive rabbits. The same antibodies, detected with a fluorescein-labeled second antibody, stained the cytoplasm of smooth muscle and certain other cells in sections of kidney, aorta, carotid artery, heart, liver, pancreas, adrenal gland, and small intestine from normal and hypertensive rabbits. We suggest that renin is converted into a form that is present most conspicuously in arterial and arteriolar smooth muscle. Its function in this location is unknown but must involve vasoconstriction as its neutralization by specific antibody lowers the blood pressure of one-kidney, one clip hypertensive rabbits.
Left ventricular wall stress and systolic function in untreated primary hypertension.
Authors: Hartford M , Wikstrand J C , Wallentin I , Ljungman S M , Berglund G L
Published: June 2012

A noninvasive investigation was undertaken in four blood pressure (BP) groups of untreated 49-year-old men derived by screening a random population sample: normotensive men (n = 20) and subjects with borderline (n = 30), mild (n = 45), or moderate BP elevation (n = 24). We here report the findings regarding left ventricular (LV) wall stress, LV wall thickness, and LV systolic function. Although there was an increase in LV wall thickness with hypertension, the raised BP was not compensated for by a sufficient degree of LV wall thickening to keep wall stress within normal limits in the hypertensive groups. Among a subset of individuals with pronounced increase in wall thickness peak systolic wall stress approached the normal range, but end-systolic wall stress was still high. In spite of high wall stress LV systolic function was normal or supranormal in the hypertensive men. The LV ejection phase indices showed a close inverse correlation with end-systolic wall stress (r = -0.67 to -0.84) in all four BP groups, but no correlation or only a weak correlation with peak systolic wall stress (r = 0.18 to -0.40). As judged from the relationship between end-systolic wall stress and ejection phase indices of LV function in the normotensive controls, all hypertensive groups had higher than expected values for LV ejection phase indices, which indicates an increased myocardial contractility secondary to adrenergic stimulation or to a more efficient contractile machinery in the myocardial cells.