bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of high and low sodium intake on arterial pressure and forearm vasular resistance in borderline hypertension. A preliminary report.
Authors: Mark A L , Lawton W J , Abboud F M , Fitz A E , Connor W E , Heistad D D
Published: June 2012

The purpose of this study was to evaluate effects of high and low sodium intake on arterial pressure and forearm vascular resistance in subjects with borderline hypertension and to compare responses to sodium excess in these subjects with responses in a recent study in normotensive subjects. Six subjects with borderline hypertension were studied after ten days of high (410 mEq/24hr) and low (10mEq/24hr) sodium intake. Potassium intake was constant. In five of six subjects, high sodium intake decreased forearm blood flow and increased forearm vascular resistance and arterial pressure. During low and high sodium intake forearm blood flow averaged 7.8 plus or minus 1.2 (SE) and 5.9 plus or minus 0.8 ml/min x 100 ml, respectively; forearm vascular resistance averaged 13.5 plus or minus 2.2 and 19.1 plus or minus 3.0 units, respectively; and mean arterial pressure averaged 89 plus or minus 3 and 98 plus or minus 2 mm Hg, respectively. High sodium intake augmented forearm vasoconstrictor responses to lower body negative pressure, a stimulus to neurogenic vasoconstriction. The results contrast with our earlier results in normotensive subjects in whom sodium excess produced forearm vasodilatation and failed to increase arterial pressure significantly. Decreases in renin and aldosterone with high sodium intake were similar in the two groups. The results suggest that excessive sodium intake in subjects with borderline hypertension produces abnormal increases in forearm vascular resistance, neurogenic vasoconstriction, and arterial pressure. The reasons for the contrast between the borderline hypertensives and normotensives are unknown, but they do not seem to be related to the renin-angiotensin-aldosterone system.
Angiotensin III: (DES-Aspartic Acid-1)-Angiotensin II. Evidence and speculation for its role as an important agonist in the renin - angiotensin system.
Authors: Goodfriend T L , Peach M J
Published: June 2012

Evidence is reviewed that three and possibly four peptides formed from renin substrate have biological activity that merits their recognition as agonists. The decepeptide angiotensin I affects sites in the central nervous system and adrenal medulla. The octapeptide angiotensin II affects vascular and cardiac sites that mediate acute pressor responses, and also causes direct feedback inhibition of renin release. The heptapeptide (des-asp-1)-angiotensin II ("angiotensin III") stimulates aldosterone release.. It may exert its effects intracellularly at the adrenal glomerulosa and other sites. The fourth candidate is the (des-asp-1)-angiotensin I nonapeptide, but nothing is known of its activity or circulating levels. This formulation of the angiotensin reaction sequence and the effects of its individual congeners suggests several experiments. It also permits simple explanations for previously confusing data, such as the inability of immunization and anti-angiotensin II to prevent aldosterone responses, and the paradoxical preservation of adrenal responsiveness in Bartter's syndrome.
Inotropic effects of different calcium ion concentration on the embryonic chick ventricle. Comparison of single cultured cells and intact muscle strips.
Authors: Barry W H , Pitzen R , Protas K , Harrison D C
Published: June 2012

The effects of changes in the calcium ion concentration in the medium bathin single beating cultured chick embryo ventricular cells were determined using an electro-optical monitoring technique for measuring the amplitude and velocity of cell wall motion. Although single cells showed significant decreases in the amplitude and velocity of cell wall motion during contraction when the calcium ion concentration was lowered from 1.8 mM to 0.9 mM, there were no significant changes in these parameters when the concentration was increased from 1.8 mM to 3.6 mM, and the magnitude of this response increased with increasing embryonic age. These results suggest that there is a reduced positive inotropic responsiveness in young chick embryo ventricular cells, which is particularly marked in the single cultured cell preparation because of the tendency of culturing techniques to select out immature cell populations.
Serotonin transport by cultured bovine aortic endothelium.
Authors: Shepro D , Batbouta J C , Robblee L S , Carson M P , Belamarich F A
Published: June 2012

Endothelial cells isolated from bovine aortas without prior treatment with enzymes were cultured in RPMI 1640 medium containing 17% fetal calf serum and antibiotics. The endothelial cells at confluency (7 days) were similar to endothelium in situ or to freshly isolated endothelial cells from blood vessels as seen by light, scanning, and electron microscopy. Cultured and freshly isolated indothelial cells exposed to labeled serotonin, even in the presence of iproniazid (5 x 10-4M), took up approximately 125 and 250 pmoles 14C-serotonin/mg protein, respectively, in 3 hours. Imipramine (10-4M) reduced uptake for both cell groups. Cold (4 degrees C) and metabolic inhibitors sharply reduced serotonin uptake by both freshly isolated and cultured endothelial cells. Ouabain (10-5M) almost completely blocked serotonin transport. Six analogues of serotonin at concentrations ten times above experimental serotonin concentrations did not affect serotonin transport in the cultured endothelial cells but did reduce it in the freshly isolated endothelial cells by 50%. The data on transport suggest that serotonin uptake is not unique to pulmonary endothelium, as has been suggested previously. In addition, using cultured indothelial cells to study serotonin transport is compatible with using other serotonin model systems such as platelets, lung, or brain. Lastly, serotonin uptake by endothelial cells may involve an active transport mechanism similar to that described for the pulmonary circulation, platelets, and insect salivary glands.
Renal prostaglandin synthesis in the Goldblatt hypertensive rat.
Authors: Pugsley D J , Beilin L J , Peto R
Published: June 2012

The role of prostaglandins in blood pressure regulation was studied in normal rats and in animals with renal artery constriction. The effects of chronic inhibition of prostaglandin (PG) synthesis on arterial pressure were observed, and renal medullary PG synthesis was measured in vitro. The prostaglandin synthetase inhibitor indomethacin was given in a dose of 2 mg/kg/day by mouth to one of two groups of male Wistar rats with a unilateral renal artery constriction and the other kidney untouched, and to one of two sham-clipped groups. Systolic blood pressures were higher in indomethacin-treated clipped rats than in non-indomethacin-treated clipped animals, and at 18 days averaged 188 mm Hg (plus or minus SEM 5.9, n = 36) and 162 mm Hg (plus or minus SEM 7.6, n = 34), respectively (P less than 0.005 for data pooled from two experiments). Indomethacin did not affect pressures of sham-clipped animals treated for 40 days. Analysis of PG synthesis by gas-liquid chromatography in renal medullary slices incubated for 30 minutes in Krebs-Henseleit buffer showed: (1) 40% suppression of PGE synthesis in hypertensive animals (P less than 0.001): (2) no differences between clipped and untouched kidneys; (3) chronic indomethacin treatment did not affect PGE synthesis in the in vitro buffer system; and (4) no PGA synthesis was detected. In a further experiment in which medullary slices were incubated in plasma of rats treated with equivalent doses of indomethacin, PGE synthesis was suppressed by 35%. The experiments support the concept that prostaglandins modulate pressor mechanisms which come into play when renal blood flow is drastically reduced. The effects could be mediated by PG synthesis in the kidney and/or in other systemic vascular beds.
Regional differences in myocardial performance in the left ventricle of the dog.
Authors: LeWinter M M , Kent R S , Kroener J M , Carew T E , Covell J W
Published: June 2012

To determine whether significant regional differences in shortening exist in the canine left ventricle, the shortening characteristics of small segments of the circumferentially oriented hoop axis fibers and the more longitudinally oriented fibers near the epicardium were examined using pairs of ultrasound crystals placed at three levels of the left ventricular free wall in the open-chest dog. Mean control shortening of the hoop axis fibers near the apex of the left ventricle averaged 20% of the end-diastolic length, significantly greater than shortening at the midventricular (13%) or basal (14%) levels. During transient periods of aortic constriction, end-diastolic length increased significantly and the extent of shortening was maintained for the hoop axis fibers at the apical and midventricular levels; end-diastolic length did not change and shortening decreased at the basal level. The epicardial fibers shortened an average of 5.6% of their end-diastolic length during control conditions at all three sites and showed small, parallel changes in shortening and end-diastolic length during aortic constriction. We conclude that significantly greater hoop axis shortening occurs near the apex of the left ventricle and that at this level a uniformly contracting model is inappropriate. In addition, the response of the hoop axis fibers to increased aortic impedance is not homogeneous, with a significant reduction in shortening occurring only at the base of the left ventricle where end-diastolic length does not increase.
Altered ion transport in aortic smooth muscle during deoxycorticosterone acetate hypertension in the rat.
Authors: Jones A W , Hart R G
Published: June 2012

Change in aortic water and electrolyte distribution and in ion turnover were studied during the development of deoxycorticosterone acetate (DOCA) hypertension in the rat. Treatment with DOCA plus saline during the prehypertensive phase was associated with increases in 42K turnover (0.0142 +/- 0.0005 vs. 0.0102 +/- 0.0003 min-1), cell water (0.89 +/- 0.03 vs 0.76 +/- 0.02 kg/kg dry weight), and the ratio of weight to length. These parameters were further increased during the development of hypertension. Significant increases were also observed in total K, Ca, and Mg contents and in Na and C1 contents corrected for the extracellular space. The turnover of 36Cl was increased (0.230 +/- 0.006 vs. 0.136 +/- 0.004 min-1) in DOCA hypertensive rats as was the content of slowly exchanging Cl. Removal of extracellular Ca greatly increased the steady-state turnover of 42K. For control rats, a Ca concentration of 0.1 mM reduced the rate of 42K turnover to less than 50% of the Ca-free value (0.063 +/- 0.004 min-1), whereas DOCA hypertensive rats exhibited only a 10% reduction. At the highest Ca concentration, 5 mM, the 42K turnover was greater in DOCA-treated rats with the hypertensives operating at 67% of maximum efflux or about twice the efflux in controls. It is concluded that significant alterations in ion transport by vascular smooth muscle occur before and during the development of hypertension induced by treatment with DOCA plus saline. Such changes may result from a reduced ability of Ca to stabilize the membrane. It is proposed that such alterations contribute to the changes in vascular reactivity and the hypertrophy associated with hypertension.
Evidence for an increase in adrenergic nerve function in blood vessels from experimental hypertensive rabbits.
Authors: Bevan R D , Purdy R E , Su C , Bevan J A
Published: June 2012

The possibility of changes in the adrenergic innervation of blood vessels in experimental hypertension was investigated by measuring arterial norepinephrine content, neuronal uptake of norepinephrine, and the neurogenic contractile response in rabbits made hypertensive by partial constriction of the abdominal aorta proximal to the kidneys. Two to 3 weeks after surgery, norepinephrine content was increased in the arteries above the ligature, where arterial blood pressure was increased, but not in the arteries below the ligature, where arterial blood pressure was normal, in the heart, or in the veins. Neuronal norepinephrine uptake per unit length of vessel and the neurogenic contractile response increased with the rise in arterial blood pressure. The neurogenic contractile response can be taken as an indication of an increase in transmitter release. The results taken together suggest an increase in the function and possibly the amount of the adrenergic neuroneal terminal in hypertension. Since the distributions of the changes in the adrenergic innervation and the increases in smooth muscle cell proliferation in hypertension are similar, these two processes may be interrelated.
Effect of coronary blood flow on glycolytic flux and intracellular pH in isolated rat hearts.
Authors: Neely J R , Whitmer J T , Rovetto M J
Published: June 2012

The rate of coronary blood flow was varied in isolated working rat heart preparations to determine its influence on the rate of glocose utilization, tissue high-energy phosphates, and intracellular pH. A 60% reduction in coronary blood flow resulted in a 30% reduction in oxygen consumption, an accelerated rate of glusoe utilization, lower tissue levels of high-energy phosphate, and higher tissue levels of lactate and H+. Ventricular performance deteriorated as reflected by a decrease in heart rate and peak systolic pressure. Further reductions in coronary blood flow resulted in inhibition of glycolysis, a greater decrease in tissue levels of high-energy phosphates, and higher tissue levels of both lactate and H+. These changes in glycolytic flux, tissue metabolites, and ventricular performance were proportional to the degree of restriction in coronary blood flow. The importance of coronary blood flow and washout of the interstitial space in the maintenance of accelerated glycolytic flux in oxygen-deficient hearts is emphasized. It is concluded that acceleration of ATP production from glycolysis can occur only in the marginally ischemic tissue in the peripheral area of tissue supplied by an occluded artery. The central area of tissue which receives a low rate of coronary blood flow will have a reduced rate of ATP production due to both a lack of oxygen and an inhibition of glycolysis.
Comparison of contractile performance of canine atrial and ventricular muscles.
Authors: Urthaler F , Walker A A , Hefner L L , James T N
Published: June 2012

This study compared the contractile performance of a canine right atrial trabecula with that of a macroscopically indistinguishable trabecula isolated from the right ventricular apex. The heart was removed from nine mongrel puppies weighing 6-8 kg and placed in Krebs-Ringer's bicarbonate solution. The bathing solution contained only 1.25 mmoles of Ca2+ and was bubbled with a 95% O2-5% CO2 gas mixture. Each atrial trabecula was specially selected from the right atrial appendage. Histologically, these trabeculae showed a remarkable longitudinal orientation of the fibers. At Lmax (the length of the muscle at which developed tension was maximum) under identical conditions of temperature, rate of stimulation, ionic milieu, pH, and O2 and CO2 supply, right atrial trabeculae achieved the same developed and total tensions but in a much shorter time than did ventricular trabeculae. In both muscle groups the maximum developed tension averaged about 2.5 g/mm2. Since Lo (expressed as a fraction of Lmax) was less in atrial muscle than it was in ventribular muscle, we concluded that atrial muscle can be stretched considerably more than can ventricular muscle before optimum length is reached. At any given initial muscle length, the maximum of tension rise for atrial trabeculae amounted to at least twice that for ventricular trabeculae. At any given load up to 1.5 g/mm2, the maximum velocity of shortening of an atrial trabecula was about three to four times that of a ventricular trabecula. These results collectively indicate that the contractile performance of the right atrial muscle is in many respects superior to that of the right ventricle, at least under the conditions of these experiments.
Baroreceptor reflex control of arterial hemodynamics in the dog.
Authors: Cox R H , Bagshaw R J
Published: June 2012

The regional differentiation of carotid sinus control of arterial pressure-flow relationships was studied in chloralose-anesthetized dogs. Simulatneous pressure-flow measurements were made in the ascending aorta, the celiac artery, the cranial mesenteric artery, the renal artery, and the femoral artery. The carotid sinuses were bilaterally isolated and perfused with pulsatile pressure. The open-loop reflex gain was not symmetrical about and was maximum at pressures below the closed loop operating point pressure. Changes in both peripheral resistance and cardiac output contributed significantly to the open-loop gain with the former predominating. Aortic impedance for frequencies above 3 Hz was at a minimum at the closed-loop operating point and increased for both higher and lower values of carotid sinus pressure. For the frequency range from 3 to 9 Hz, regional impedance in all of the beds varied inversely with carotid sinus pressure. The sensitivity of the various beds to changes in carotid sinus pressure around the operating point increased in the order celiac less than mesenteric less than renal less than femoral. Following vagotomy, operating point values of regional resistance and sensitivity were significantly increased. This fact suggests that the aortic arch receptors exert a significant influence on regional vascular impedance at operating point pressures. The fraction of cardiac output in the celiac, mesenteric, and renal beds was nearly independent of carotid sinus pressure before and after vagotomy, but that in the femoral bed increased with carotid sinus pressure. These results demonstrate the nonuniform nature of carotid sinus and aortic arch baroreceptor control of regional blood flow.
Facilitation of adrenergic transmission by locally generated angiotensin II in rat mesenteric arteries.
Authors: Malik K U , Nasjletti A
Published: June 2012

When studied on isolated rat mesenteric arteries perfused with Tyrode's solution, angiotensin I and angiotensin II (1 ng/ml), a synthetic tetradecapeptide renin substrate, and a purified hog renin substance (50-100 ng/ml) potentiated vasoconstrictor responses to sympathetic nerve stimulation and to injected norepinephrine without altering basal pressure. These agents produced a greater augmentation of the vasoconstrictor responses to nerve stimulation than to injected norepinephrine. The potentiation of vasoconstrictor responses to sympathetic nerve stimulation and injected norepinephrine which was elicited by renin substrate and angiotensin I was abolished by an inhibitor of angiotensin I-converting enzyme, SQ 20,881, and by an angiotensin II receptor antagonist, [Sar1-Ile8]angiotensin II. In contrast, the potentiating effect of angiotensin II was blocked only by the latter compound. We conclude that utilization of renin substrate within the vascular wall by renin or renin-like enzymes results in the formation of angiotensin I, which is converted to angiotensin II. Angiotensin in turn potentiates the vasoconstrictor responses to adrenergic stimuli presumably by augmenting release of the adrenergic transmitter and inhibiting its neuronal reuptake as well as by increasing vascular reactivity to norepinephrine.
Inhibition of prostaglandin E2 secretion. Failure to abolish autoregulation in the isolated dog kidney.
Authors: Kaloyanides G J , Ahrens R E , Shepherd J A , DiBona G F
Published: June 2012

We studied the role of renal prostaglandins in the regulation of glomerular filtration rate (GFR) and renal blood flow (RBF) in the isolated dog kidney. Indomethacin or meclofenamate, 2 mg/kg of body weight, suppressed renal prostaglandin E2 (PGE2) secretion, measured by radioimmunoassay, to zero within 20 minutes; the effect persisted for the duration of the study. When renal arterial pressure (PRA) was maintained at 104 mm Hg both drugs caused a sharp decrease in sodium excretion and RBF with redistribution of flow from inner to outer cortes we examined autoregulation of GFR and RBF over the pressure ranges of 150-100 and 150-75 mm Hg, respectively, after inhibition of PGE2 secretion and under control conditions. deltaGFR/deltaPRA (ml/min per mm Hg) was 0.020 +/- 0.017 in the indomethacin group, 0.152 +/- 0.055 in the meclofenamate group, and 0.086 +/- 0.017 in the control group. The change in GFR for the indomethacin group was significantly less than that for meclofenamate (P less than 0.01) and control groups (P less than 0.025); the latter two groups were not statistically different from each other (P greater than 0.1). There was no significant difference (P greater than 0.1) between the three groups with respect to deltaRBF/deltaPRA, which measured 0.288 +/- 0.046, 0.370 +/- 0.112, and 0.438 +/- 0.123 ml/min per mm Hg in the indomethacin, meclofenamate and control groups, respectively. Renal was lowered from 150 to 75 mm Hg. The observation that inhibition of prostaglandin synthesis promotes a redistribution of RBF from inner to outer cortex suggests that renal prostaglandins may participate in the regulation of medullary blood flow. However, since autoregulation of GFR and RBF remained intact despite inhibition of prostaglandin secretion, these data argue against a role for renal prostaglandins in regulating whole kidney GFR and RBF.
Changes in cyclic nucleotide levels and contractile force in the isolated hypoxic rat heart during perfusion with glucagon.
Authors: Busuttil R W , Paddock R J , Fisher J W , George W J
Published: June 2012

Isolated rat hearts were perfused with hormonal concentrations of glucagon during a hypoxic perfusion to determine whether it would enhance recovery after reoxygenation. Rat hearts were divided into two groups: (1) those perfused with glucose-free Tyrode's solution and (2) those perfused with Tyrode's solution containing glucose. During 3 minutes of exposure to hypoxia both untreated hearts and hearts perfused with glucagon demonstrated a decrease in contractile force to 10-20% of control. When glucose was present in the perfusion medium, cardiac performance was better during both the periods of hypoxia and reoxygenation. During reoxygenation, recovery of contractile force was significantly better (P less than 0.05) in glucagon-perfused hearts than in untreated hearts; this improved recovery occurred regardless of whether glucose was included in the medium. The enhanced recovery of the glucagon-perfused hearts was associated with decreases in myocardial levels of guanosine, 3',5'-monophosphate (cyclic GMP) both during the periods of hypoxia and reoxygenation. At the end of the hypoxic period, cyclic GMP levels in the glucagon-perfused hearts were 20-64% of the levels in untreated hearts. Similarly, after 5 minutes of reoxygenation cyclic GMP levels in the glucagon-perfused hearts were 21% of the levels in the untreated hearts. The effect of glucagon on adenosine 3',5'-monophosphate (cyclic AMP) concentrations in untreated hearts and in hearts receiving glucagon was not significantly different either after 3 minutes of hypoxia or during reoxygenation. The rate of anaerobic glycolysis after 3 minutes of hypoxia was higher in untreated hearts than in glucagon-perfused hearts, as determined by the lactate content of coronary perfusates. These studies suggest that hormonal concentrations of glucagon exert a protective effect on the hypoxic rat heart which involves a modulation of cardiac cyclic GMP accumulation.
The effect of lidocaine on diastolic transmembrane currents determining pacemaker depolarization in cardiac Purkinje fibers.
Authors: Weld F M , Bigger J T
Published: June 2012

We studied the effects of lidocaine (1-5 mg/liter) on the diastolic currents of sheep Purkinje fibers by the two-microelectrode voltage clamp technique to obtain additional information on how lidocaine decreases the slope of spontaneous diastolic depolarization of mammalian Purkinje fibers. During voltage clamps we measured both the magnitude and time course of activation and deactivation of the time- and voltage-dependent potassium "pacemaker current" (iK2), and also the steady state current-voltage relationship throughout the pacemaker voltage range. At a concentration of 1 mg/liter lidocaine had no effect on the amplitude of iK2. In contrast, at 5 mg/liter, lidocaine diminished the magnitude of iK2 throughout the voltage range of pacemaker depolarization. Lidocaine (1-5 mg/liter) had no effect on either (1) the transmembrane voltage at which iK2 is half-activated, (2) the reversal voltage for iK2, or (3) the kinetics of iK2. Lidocaine (1-5 mg/liter) increased the steady state outward transmembrane current. This effect of lidocaine can be attributed to a variable contribution from both an increase in time-independent outward potassium current (iK1) and a decrease in background inward current.
Reflex suppression of renin secretion during distention of cardiopulmonary receptors in dogs.
Authors: Zehr J E , Hasbargen J A , Kurz K D
Published: June 2012

We studied the effect of brief periods of left atrial-pulmonary vein distention on the rate of renin secretion in sodium-restricted dogs anesthetized with chloralose and breathing spontaneously. Series 1 consisted of 32 trials in seven dogs with intact renal nerves and intact vagi. Renin secretion, calculated as the product of renal venous minus arterial renin activity (radioimmunoassay) times renal plasma flow (electromagnetic flowmeter), was depressed to 56% of control during atrial distention despite no change in arterial pressure, central venous pressure, or renal blood flow. Series 2 consisted of 58 trials in 12 dogs which had undergone unilateral renal denervation several days prior to the studies. Simultaneous, bilateral determinations indicated that renin secretion from the innervated kidney was depressed to 58% of control during atrial distention; secretion from the denervated kidney was unchanged. Series 3 consisted of 30 trials in six dogs with bilateral cervical vagotomy. Atrial distention evoked no changes in renin secretion. We conclude that left atrial distention reflexly reduces the rates of renin secretion via vagal afferent and renal sympathetic efferent pathways.
Effects of activation sequence on the local recovery of ventricular excitability in the dog.
Authors: Abildskov J A
Published: June 2012

We measured refractory periods at ventricular sites in the dog heart during drive from ventricular test sites and during combined drive from the test sites and other ventricular sites or the atrium. We found that ventricular activation sequence caused significant alterations on refractory period. Combined drive from two sites which resulted in fusion complexes was associated with shorter refractory periods at the test sites than those observed during drive at the test sites only. Our findings are explicable because earlier excitation and consequent earlier recovery of surrounding areas during fusion beats exerts an electrotonic influence on test sites.
Effect of thoracic blood volume changes on steady state cardiac output.
Authors: Mitzner W , Goldberg H , Lichtenstein S
Published: June 2012

We have investigated the extent to which shifts of blood volume out of or into the thoracic region influence the steady state cardiac output. The systemic circulation of anesthetized dogs was replaced with an artificial circuit which stimulated the pertinent mechanical characteristics of an intact circulation. As in the normal animal, the steady state venous return was proportional to the pressure gradient for venous return (i.e, mean systemic minus right atrial pressure). Cardiac function was altered either by administration of epinephrine or by changes in left ventricular afterload. At a constant mean aortic pressure of 100 mm Hg, epinephrine administration increased the steady state cardiac output by 55%. Half of this increase resulted from the lowered mean right atrial pressure (caused by improved cardiac function); the remainder resulted from an increased mean systemic pressure (caused by the volume shift to the systemic circulation). Increases in afterload transferred sufficient volume to the heart-lung compartment to reduce significantly the mean systemic pressure and, hence, the steady state venous return. Our results indicate that the heart-lung compartment contains a significant volume which is under cardiac control. In addition to being able to alter the right atrial pressure, the heart can modulate the steady state cardiac output by adjusting the mean systemic pressure. To this degree the heart can adjust its own venous return.
Blood pressure and plasma angiotensin II concentration after renal artery constriction and angiotensin infusion in the dog. (5-Isoleucine)angiotensin II and its breakdown fragments in dog blood.
Authors: Caravaggi A M , Bianchi G , Brown J J , Lever A F , Morton J J , Powell-Jackson J D , Robertson J I , Semple P F
Published: June 2012

We measured arterial plasma angiotensin II concentration, renal blood flow, and arterial blood pressure in six conscious dogs during intravenous infusion of angiotensin II (5, 10, and 20 ng/kg per min). The same measurements were made on a different occasion in the same six animals, while they were conscious, before and during constriction of a main renal artery. Arterial blood pressure and plasma angiotensin II rose and renal blood flow decreased in both experiments. The similarity of regressions for plasma angiotensin II concentration and arterial blood pressure in the two experiments strongly suggests that the rise of circulating angiotensin II after renal artery constriction is sufficient to account for the hypertension by its direct pressor action. As discussed, a different mechanism seems likely to be involved in the later stages of renal hypertension. Angiotensin II is more likely to be in the 5-isoleucine form than in the 5-valine form in the dog. In contrast to the rat, plasma concentrations of the heptapeptide (angiotensin III), hexapeptide, and pentapeptide fragments of angiotensin II are low in the dog.
The role of arterial baroreceptors in mediating the cardiovascular response to a cardiac glycoside in conscious dogs.
Authors: McRitchie R J , Vatner S F
Published: June 2012

To determine the role of the arterial baroreceptor reflex in mediating the cardiovascular response to a cardiac glycoside, we examined the effects of ouabain (G-strophanthin), 17.5 mug/kg, iv, on direct and continuous measurements of left ventricular diameters, pressures, velocity of shortening, (dP/dt)/P, arterial pressure, cardiac output, and total peripheral resistance. These studies were conducted on healthy conscious dogs before and after total arterial baroreceptor denervation (TABD). Maximal pressor effects were observed in the first 3-5 minutes; mean arterial pressure increased by 11 +/- 1 mm Hg in normal dogs compared to 33 +/- 4 mm Hg in denervated dogs. In intact dogs at this time heart rate decreased by 18 +/- 2 beats/min and cardiac output fell by 18 +/- 3%; these values gradually returned toward control over 15-30 minutes. When heart rate was kept constant, cardiac output did not fall after injection of ouabain. In contrast, heart rate and cardiac output did not change significantly after ouabain in dogs with TABD. The maximal effects on the contractile state of the heart occurred between 15-30 minutes and were similar in both groups. Arterial baroreceptor reflexes appear to be responsible for the reduction in heart rate and cardiac output caused by administration of ouabain to the intact dog. They exert an important buffering action on the vasopressor effect but a less important action on the inotropic response.
Maintained stroke volume but impaired arterial oxygenation in man at high altitude with supplemental CO2.
Authors: Grover R F , Reeves J T , Maher J T , McCullough R E , Cruz J C , Denniston J C , Cymerman A
Published: June 2012

Hypobaric hypoxia causes hypocapina and alkalosis, hemoconcentration and increased hematocrit, and a decreased cardiac stroke volume. To assess the role of the hypocapnic alkalosis in causing these other changes, five men were exposed to hypobaric hypoxia at a barometric pressure (PB) of 440 torr with an alveolar O2 tension of 55 torr for 5 days with 3.77% CO2 added to the atmosphere to prevent alkalosis. They did not lose weight, and arterial CO2 tension, pH, and cardiac stroke volume were unchanged. An unchanged hematocrit implied an unchanged plasma volume. During exercise to maximum, stroke volumes equaled sea level values but arterial hypoxemia was profound, the arterial O2 tension being 39 torr. By contrast, three men at high altitude without CO2 supplementation (PB=455 torr; alveolar PO2=56 torr) had weight loss, hypocapnia, alkalosis, and decreased stroke volume. Increased hematocrits suggested decreased plasma volumes. During exercise, arterial PO2 (48 torr) was higher than in the group receiving CO2. Maximum oxygen uptakes were decreased to a similar degree in the two groups. Catecholamine excretion doubled in the group with CO2 but in the group without CO2 catechoamine excretion was unchanged. A normal pH at high altitude apparently maintained plasma volume, which, with the increased catecholamine excretion, may have prevented a decrease in stroke volume. However, the subjects with CO2 added did not have enhanced oxygen transport, because their arterial oxygenation was impaired.
The role of angiotensins in aldosterone production.
Authors: Bravo E L , Khosla M C , Bumpus F M
Published: June 2012

The hypothesis that the COOH-terminal heptapeptide mediates the aldosterone-stimulating activity of angiotensin II was evaluated by comparing the relative effects on aldosterone production of angiotensin II and the heptapeptide to angiotensin analogues that are poorly metabolized to the heptapeptide and to a nonapeptide, des-Asp-1-angiotensin I, that is directly converted to the heptapeptide. In in vivo studies utilizing the adrenocorticotropic hormone-suppressed bilaterally nephrectomized dog, angiotensin II and the heptapeptide produced statistically significant increases in both aldosterone and cortisol secretory rates (P less than 0.001 for both relations). Sar-1-angiotensin II stimulated the production of both steroids to the same extent, but had much longer duration of action. [Poly(oAc)Seryl]angiotensin II was a weak agonist, having only about 30% of the steroidogenic potency of either angiotensin II or the heptapeptide. In equimolar concentrations des-Asp-1-angiotensin I had about one-half of the aldosterone-stimulating activity of the hepatpeptide. In in vitro studies, employing the trypsin-dispersed cat adrenal zona glomerulosa cells, the steroidogenic potency of angiotensin II and the heptapeptide was identical to maximal aldosterone production of 10(-8) M peptide concentration. By contrast, the response to Sar-1-angiotensin II was approximately a 10-fold increase in relative potency, while the response to [poly(oAc)Seryl]angiotensin II demonstrated a 10-fold decrease. These findings suggest that, although the heptapeptide may play an important role in the regulation of aldosterone production, the possibility remains open that angiotensin II could stimulate aldosterone biosynthesis without prior conversion to the heptapeptide.
Changes in cardiovascular and adrenal cortical responses to angiotensin III induced by sodium deprivation in the rat.
Authors: Peach M J , Sarstedt C A , Vaughan E D
Published: June 2012

The restriction of dietary sodium intake is known to depress the cardiovascular responses to angiotensin II and increase the sensitivity of the adrenal zona glomerulosa to this steroidogenic octapeptide. In sodium-repleted animals, angiotensin III is a weak pressor substance and a potent stimulant of aldosterone biosynthesis. The effect of a low sodium diet on vascular and steroidogenic responses to angiotensin II and angiotensin III was investigated. In nephrectomized rats, angiotensin III had one-third of the pressor activity relative to angiotensin II when either normal or sodium-deprived animals were compared. When administered subcutaneously (sc) to rats, angiotensin II and III induced comparable steroidogenic responses, whereas only angiotensin II significantly elevated blood pressure. The comparison of cell suspensions from control adrenals with suspensions of adrenals from sodium-deprived animals showed that the zona glomerulosa from rats on low sodium diets had increased wet weight (20%), cell protein (25%), and basal steroidogenic rats (45%). Adrenocorticotropic hormone (ACTH)-induced responses in adrenal cells from low sodium animals were about twice the responses of cells from normal adrenals. Angiotensin II and III stimulated the cortex at a threshold concentration of 5 X 10(-10) M and induced a maximum response at about 5 X 10(-8) M in cells prepared from normal rat adrenals. In cells dispersed from adrenal capsules of sodium-deprived rats, the maximal steroidogenic response to angiotensin II occurred at 3 X 10(-8) M, whereas angiotensin III was maximal at 1 X 10(-9) M. Aldosterone synthesis induced by both peptides was increased approximately 45% in adrenal cells from low salt rats. At 0.9 mumol/kg, sc, Sar-1, Ile-8-angiotensin II antagonized cardiovascular responses to angiotensin II and did not alter aldosterone in the sodium-deprived rat. In contrast, treatment with Ile-7-angiotensin III blocked the adrenal cortex but not the vascular actions of angiotensin II. These data are consistent with a role for angiotensin III in the renin-angiotensin-aldosterone response to sodium deprivation.
Interactions between sino-aortic reflexes and cardiovascular effects of sleep and emotional behavior in the cat.
Authors: Baccelli G , Albertini R , Mancia G , Zanchetti A
Published: June 2012

The role of sino-aortic reflexes in the control of circulation during normal behavior was investigated by comparing cardiovascular reactions during various but reproducible types of behavior before and after bilateral sino-aortic deafferentation. Chronic deafferentation caused little change in baseline blood pressure, but a subtler, important role of sino-aortic reflexes was revealed by examining the integrated cardiovascular responses to behavioral stimuli. During desynchronized sleep, the buffering action of sino-aortic reflexes prevented a marked and diffuse vasodilation, with an action that was particularly evident on muscle blood vessels. During emotional behavior, especially when emotion was accompanied by movement, sino-aortic reflexes opposed the consequences of muscle vasodilation by inducing tachycardia and vasoconstriction in the viscera and in noncontracting muscles. A reciprocal type of interaction between behavior and sino-aortic reflexes was shown by testing the amplitude of the carotid occlusion response before and during desynchronized sleep; the latter condition was consistently associated with decreased effectiveness of the reflex response. The possibility is considered that this might indicate central suppression of the carotid sinus reflex during desynchronized sleep and that a similar inhibitory interference might occur during emotional behavior. Alternatively, reduction of the reflex response might result from a shift of the stimulus-response curve on either side of its steep portion.
Relation between plasma renin activity, angiotensin, and aldosterone and blood pressure in mild untreated hypertension.
Authors: Walker W G , Horvath J S , Moore M A , Whelton P , Russell R P
Published: June 2012

Plasma renin activity, arterial and venous angiotensin II (A II), plasma aldosterone, and sodium excretion were measured in a group of 101 patients with mild essential hypertension. For the total hour; arterial A II was 5.2 +/- 1.0 pg/ml; venous A II was 4.2 +/- 0.6 pg/ml; and plasma aldosterone was 5.0 +/- 0.45 ng/100 ml. All values were lower corresponding values for normal subjects on a high salt intake despite the fact that salt intake in the normal subjects exceeded that for the hypertensive group more than 3-fold. Moreover, when the range of diastolic blood pressure up to 114 mm Hg was divided into three successive class intervals of increasing severity, there was a negative correlation between diastolic blood pressure and both PRA and plasma aldosterone. Arterial A II showed an anomalous increase in the class interval 105-114 mm Hg, despite the fact that this group exhibited the lowest level of PRA. At diastolic blood pressures above 114 mm Hg, the PRA appears to rise again. The anomalous increase in arterial A II in the presence of marked suppression of PRA is consistent with the presence of a renin activator or accelerator factor in hypertensive plasma as postulated by others. It also identifies a possible mechanism whereby even small increases in PRA could exert an adverse effect on the hypertensive state.
Arterial and venous angiotensin II in normal subjects. Relation to plasma renin activity and plasma aldosterone concentration, and response to posture and volume changes.
Authors: Walker W G , Moore M A , Horvath J S , Whelton P K
Published: June 2012

Plasma renin activity, arterial and venous angiotensin II (A II) concentrations, and plasma aldosterone concentration were measured in 16 normal subjects (mean age = 34 years) after 8 hours of recumbency, following 2 hours of ambulation, and again 30 minutes after administration of furosemide intravenously. Measurements were obtained during periods of sodium restriction and again during sodium surfeit. Both arterial and venous A II exhibited a 3-fold increase from low values of 8.8 +/- 2.5 and 8.6 +/- 2.5 pg/ml of plasma, respectively, during recumbency on high sodium intake to values of 23.9 +/- 4.1 and 26.5 +/- 6.2 pg/ml, respectively, following intravenous furosemide during sodium restriction. Corresponding values for aldosterone exhibited a 5-fold rise from 5.6 ng/100 ml to 32.0 ng/100 ml, whereas plasma renin activity (PRA) measured by an in vitro assay exhibited a 20-fold rise from 0.6 +/- 0.2 ng of angiotensin I (AI) generated per ml per hour to 13.1 ng/ml per hour. Despite the disparity in the magnitude of these increases, significant correlations were identified between all four of the measured parameters, indicating a major role of the renin-angiotensin system in regulating aldosterone output in response to volume and posture-related stimuli. Values of arterial and venous immunoreactive A II were closely correlated ( r = +0.72, P less than 0.005), but significant differences were demonstrated between low and high salt periods, suggesting that changes in metabolism of A II in the peripheral circulation may occur during sodium restriction.
Plasma renin activity during exercise in the dog.
Authors: Lifschitz M D , Horwitz L D
Published: June 2012

Previous workers have suggested that a rise in plasma renin activity (PRA) may mediate some of the hemodynamic changes associated with exercise. To test this hypothesis in nine dogs chronically instrumented for measurement of aortic pressure (catheter) or cardiac output (ascending aorta electromagnetic flow probe) PRA was measured by radioimmunoassay in blood samples drawn before and during running on a level treadmill at 4-8 miles per hour. Exercise caused increases in heart rate from 96 +/- 5 (SE) to 186 +/- 7 beats/min, cardiac output from 2.8 +/- 0.3 to 6.2 +/- 0.6 liters/min, and mean aortic pressure from 115 +/- 5 to 132 +/- 5 mm Hg (P less than 0.01). Mean PRA was 6.6 +/- 0.7 (SE) ng of angiotensin 1/ml per 3 hours before and 7.6 +/- 1.2 ng Ang I during exercise, values that are not different statistically. Propranolol reduced PRA at rest from 8.6 +/- 1.1 to 5.9 +/- 1.1 ng Ang 1 (P less than 0.05), but there was no significant difference between resting and exercise levels, although the increments in heart rate, cardiac output, and mean aortic pressure were reduced. Standing on hindlimbs for 5 minutes did not cause a change in mean aortic pressure or PRA. However, administration of pentolinium reduced mean aortic pressure, and PRA rose from 6.0 +/- 1.1 to 9.8 +/- 1.5 ng Ang I. Exercise, with or without beta-adrenergic blockade, does not cause increased PRA in conscious dogs in which the renin-angiotensin system is normally responsive.
Cutaneous and muscular rasodilation in the canine hindlimb evoked by central stimulation.
Authors: Lang W J , Bell C , Conway E L , Padanyi R
Published: June 2012

Using stereotaxic procedures, we electrically stimulated specific sites in the hypothalamus and midbrain of anesthetized dogs pretreated with guanethidine and atropine methonitrate. A tract in which stimulation caused noncholinergic dilator responses in the hindlimbs was identified. The course of this trace was different from that subserving cholinergic vasodilation in the hindlimb musculature. In a number of experiments we studied the proportional distribution of blood flow to leg and paw. Responses restricted to the paw were regarded as occurring mainly in cutaneous vessels; those restricted to the leg were regarded as occurring mainly in the skeletal muscle vessels. Some dilator responses in both beds were abolished by intra-arterial administration of antihistamines: other dilator responses were abolished by intra-arterial injections of dopamine antagonists. Centrally evoked dilation of leg and paw vessels by noncholinergic pathways suggests physiological roles for these fibers in the regulation of cardiovascular function.
Hemodynamic role of extracellular fluid in hypertension.
Authors: Tarazi R C
Published: June 2012

Plasma volume is usually lower in patients with essential hypertension than in normal subjects. Normal or expanded plasma volume in some hypertensive patients may respect either a specific hypervolemic subset of the disease or the upper end of a continuum of volume values. Difficulties in defining these groups stem from the small numbers of subjects studied, from the need for a reliable reference index for volume measurements, and from the multiple factors which may affect intravascular volume. Differences in plasma volume cap influence choice of antihypertensive therapy; patients with expanded volume tend also to have slightly exchangeable sodium and greater extracellular fluid (ECF) volume and to respond well to diuretic therapy. There is also some evidence that low plasma renin activity is more frequent among hypervolemic patients. Essential hypertensives as a group have low plasma to interstitial fluid volume ratio (PV/IF), indicating that ECF distribution between the intravascular and interstitial compartments is shifted toward the latter. This is probably related to altered capillary filtration pressure due to increased venous resistance. Hypovolemic essential hypertensives have significantly lower (P less than 0.01) PV/IF ratio than hypervolemic, but whether this is related to differences in neural venous tone is only speculative. Hemodynamic studies revealed no difference in cardiac output between hypertensive patients with contracted blood volume and those with hypervolemia; total peripheral resistance was even higher in the latter, suggesting that "vasoconstriction" is not different between the two groups. It is widely believed that the relationship between ECF expansion and hypertension depends on the development of hypervolemia, increased cardiac output, and subsequent rise in total peripheral resistance reducing volume expansion and normalizing systemic flow while maintaining a high blood pressure. This sequence of events has been demonstrated in some human and experimental forms of hypertension but not in all. Metyrapone-induced hypertension in dogs could be sustained for up to 6 weeks by increased output with no evidence of "autoregulation" developing, and similar observations were reported in some anephric patients. Complementing these findings are observations of elevated cardiac output in some patients with long-standing essential hypertension or primary aldosteronism. It is therefore suggested that the spectrum of hemodynamic changes associated with volume disturbances in hypertension is too wide to be forced under one hypothesis alone and that neurogenic and other factors may play an important role in that complex relationship.