bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of inhibitors of prostaglandin synthesis on renal vascular resistance and on renal vascular responses to vasopressor and vasodilator agents in the cat.
Authors: Chapnick B M , Paustian P W , Feigen L P , Joiner P D , Hyman A L , Kadowitz P J
Published: June 2012

We determined the effects of indomethacin and meclofenamate, two inhibitors of prostaglandin synthesis, on renal vascular resistance and on renal responses to nerve stimulation, pressor and depressor hormones in the in situ feline kidney under conditions of controlled blood flow. Both inhibitors produced a gradual rise in renal vascular resistance which became maximal 15-20 minutes after administration. The increase in renal resistance after indomethacin was not attenuated during intrarenal infusion of either phentolamine or SQ 20881. Pretreatment with propranolol, in a dose sufficient to inhibit renin secretion, also did not attenuate the increase in renal resistance produced by indomethacin. However, infusion of [Sar1-, Ala8]angiotensin II, an angiotensin II antagonist, did attenuate the indomethacin-induced increase in renal vascular resistance. After indomethacin, the vasoconstrictor response to norepinephrine was enhanced, whereas responses to nerve stimulation and angiotensin were unaffected. Although meclofenamate enhanced renal vascular resistance, its effects on vasoconstrictor responses were inconsistent. After indomethacin, the renal dilator response to bradykinin was enhanced; however, dilator responses to nitroglycerin were unaltered. The present data indicate that the increase in renal vascular resistance after indomethacin does not depend on the adrenergic system but may be dependent on the renin-angiotensin system. The inconsistent effect of the inhibitors of synthesis on renal constrictor responses to nerve stimulation suggests that endogenous prostaglandins do not serve to modulate the effects of the sympathetic nervous system on the feline renal vascular bed. These results also indicate that renal dilator responses to bradykninin are not mediated by prostaglandins in the cat.
Volume changes in sarcoplasmic reticulum of rat hearts perfused with hypertonic solutions.
Authors: Page E , Upshaw-Earley J
Published: June 2012

To explore whether morphometry of intracellular membrane-limited subcompartments can be used to follow physiological volume changes in such subcompartments in hearts rapidly fixed by perfusion fixation, we have measured osmotically induced volume changes in electron micrographs of longitudinally oriented sarcoplasmic reticulum (LSR) and terminal cisterns (TC) of rat left ventricular myocardial cells. Vascular perfusion with solutions whose osmolality varied from 0.67 to 1.88 isomolal showed that in the hyperosmolal range LSR volume decreased linearly. Approximately 79% of LSR luminal volume participated in the osmotic rey unresponsive. By contrast, we found that the TC responded by dilation when hearts were perfused with hypersomolal NaCl, NaI, LiCl, or sucrose. Furthermore, with hyperosmolal NaCl the dilation developed within 1 minute; its rate and extent of development were concentration-dependent; it manifested an obligate association with prior or concomitant T-tubular dilation and was not readily reversible. We conclude that (1) the technique sensitively measures in situ changes of LSR volume; (2) most of LSR luminal water is osmotically responsive, but a significant fraction may not be; (3) exposure to hyperosomolal solutions may bring about (perhaps irreversible) structural changes in the diadic membrane complex, leading to changes in its solute permeability.
Length-dependent calcium inotropism in cat papillary muscle.
Authors: Huntsman L L , Stewart D K
Published: June 2012

We studied changes in the relationship of isometric developed force to muscle length when extracellular calcium concentration was altered in isolated cat papillary muscles. In two series of experiments at temperatures of 30 degrees C and 32 degrees C, and rates of 12 and 30 beats/min, 21 muscles were exposed to calcium concentrations of 1.125, 2.25 and 4.5 mM. Muscle lengths were varied between 80% and 100% of the length at which maximum developed force occurred (Lmax). Peak developed force and the time from stimulus to peak were measured. The data indicate that force is not altered proportionately at all lengths when calcium concentration is changed. Rather, we found that a substantially greater modification of force occurs at short lengths than at long lengths. Similarly, the time to peak force increases with length at a rate which is more than 4 times greater at the low calcium concentration than it is at the high concentration. Small but consistent shifts of Lmax also are seen. We observed that Lmax is longer when inotropic changes reduce force and shorter when force is increased. These results indicate that the inotropic effect of extracellular calcium concentration changes is dependent on muscle length.
Renal cortical blood flow distribution in obstructive nephropathy in rats.
Authors: Siegel N J , Feldman R A , Lytton B , Hayslett J P , Kashgarian M
Published: June 2012

To examine the role of intrarenal hemodynamics in in obstructive nephropathy, we determined cortical blood flow distribution (CBFD) in rats with bilateral ureteral occlusion (BUO) and unilateral ureteral occlusion (UUO) during and after release of obstruction. Prior to release of obstruction of 24 hours' duration, we found that outer cortical perfusion decreased by 20+/-5% in both BUO and UUO rats. Furthermore, one hour after release of BUO, there was rapid normalization of CBFD associated with a modest return of glomerular filtration rate (GFR), an almost complete return of renal blood flow (RBF), and a marked postobstructive diuresis. In contrast, after release of UUO, we observed that outer cortical perfusion remained decreased by 21+/-31%, both GFR and RBF remained markedly depressed, and no diuresis occurred. These data demonstrate (1) marked ischemia of the outer cortex in both BUO and UUO during obstruction, (2) a rapid return of CBFD to a normal pattern after release of BUO, but (3) persistent outer cortical ischemia following release of UUO.
Directional coronary collateral growth with chronic circumflex occlusion in the dog.
Authors: Scheel K W , Rodriguez R J , Ingram L A
Published: June 2012

The object of this study was to determine whether coronary collateral resistances were dependent on the direction of perfusion and to investigate whether a pattern of collateral growth with gradual circumflex occlusion could be discerned. In 12 dogs an Ameroid occluder was placed on the circumflex for 1 month, and six dogs for 3 months; 12 dogs served as controls. The circumflex, left anterior descending, and right coronary arteries were separately but simultaneously perfused in an isolated heart preparation in which the vasculature was maximally dilated with dipyridamole. Collateral flows were determined by measuring retrograde flows for two vessels simultaneously. The results showed that collateral flows from the right to the left coronaries in control dogs were 3.5-fold larger than when these collateral beds were perfused in the opposite direction. This difference in the 1- and 3-month Ameroid groups was approximately 20-fold. Relative to the control group, the collateral resistances from right to left coronary vessels were an average of 10-fold less in the 1- and 3-month groups, but there was no significant differences in resistance in the collaterals perfused from the left to the right. The results strongly suggest that collateral proliferation occurs in response to hypoxia rather than to a pressure gradient, and that collateral development is toward the hypoxid area.
Contractile and biochemical responses of cardiac and skeletal muscle to isoproterenol covalently linked to glass beads.
Authors: Ingerebretsen W R , Becker E , Friedman W F , Mayer S E
Published: June 2012

The effects of (-)-isoproterenol covalently linked to glass beads on inotropic state, cyclic AMP concentration, and phosphorylase b to a conversion was studied in cat and guinea pig papillary muscles. Biochemical responses also were measured in mouse diaphragm sections. In cat papillary muscles under normal conditions and in guinea pig muscles partly depolarized with 22 mM K+ an increased inotropic state and phosphorylase activation could be dissociated from the formation of cyclic AMP. This contrasts with close correlation reported between isometric tension and cyclic AMP concentration in guinea pig papillary muscles exposed to varying concentrations of isoproterenol dissolved in the bath medium. The cyclic nucleotide did increase in guinea pig papillary muscles exposed to a freshly prepared batch of isoproterenol beads and in the mouse diaphragms. The type and age of the bead preparation had marked effects on all responses that were measured and on the rate of leakage of biologically active products from the beads. Nevertheless, experimental conditions could be obtained under which the initiation of the contractile and biochemical responses was probably limited to intense stimulation of receptors at or near the points of contact between beads and muscle and not due to gross leakage into the bath. The results indicate that cyclic AMP is probably involved in the initiation but not the propagation of the inotropic response of papillary muscles exposed to isoproterenol glass beads.
The effect of ouabain, dinitrophenol, and lithium on the pacemaker current in sheep cardiac Purkinje fibers.
Authors: Aronson R S , Gelles J M
Published: June 2012

We studied the effect of ouabain and other inhibitors of the Na-K pump on the pacemaker current (IK2) in sheep cardiac Purkinje fibers. We found that exposure to ouabain (2 X 10(7) M) caused an apparent decrease in the amplitude of the IK2 activation curve. We also found that a similar effect was caused by exposure to dinitrophenol (DNP) or lithium-substituted Tyrode's solution. Our studies showed that after prolonged (more than 60 minutes) exposure to ouabain a characteristic current noise appeared and IK2 was replaced by an oscillatory inward current (IOS). The apparent threshold for IOS was -50 to -60 mV and the peak amplitude of this current increased with increasing levels of depolarization positive to threshold. These results suggest that (1) the apparent decrease in IK2 may be a consequence of ionic redistribution due to Na-K pump inhibition; (2) cardiac glycosides cause abnormal impulse generation by an ionic mechanism separate from IK2 and involving IOS.
Myocardial function and coronary blood flow response to acute ischemia in chronic canine diabetes.
Authors: Haider B , Ahmed S S , Moschos C B , Oldewurtel H A , Regan T J
Published: June 2012

To examine the influence of preexistent diabetes mellitus on left ventricular performance and coronary blood flow responses to acute ischemia, mild normoglycemic diabetes was induced in nine mongrel dogs after three doses of alloxan, (20 mg/kg, iv), at monthly intervals. Hemodynamic measurements and coronary blood flow (85Kr clearance) were obtained before and after the onset of ischemia. This was produced by occlusion of the proximal left anterior descending coronary artery via a balloon-type catheter in nine intact anesthetized diabetic dogs and 10 nondiabetic dogs. During the 1st hour of ischemia in the diabetic group, the end-diastolic pressure rose from 7 +/- 1.1 (mean +/- SE) mm Hg to 23.8 +/- 2.3 without a significant increase of end-diastolic volume. In controls end-diastolic pressure rose from 8.6 +/- 1.1 mm Hg to 15.3 +/- 1.4, and end-diastolic volume was significantly increased, so that the ratio of end-diastolic pressure and volume was significantly higher in the diabetic group (P less than 0.005). Although indices of contractility did not differ, stroke volume and work reductions were significantly greater in diabetics, despite the fact that coronary blood flow was reduced to a similar extent. Size of the ischemic areas appeared comparable as judged by distribution of dye injected distal to the occlusion. Since potassium loss and sodium gain in the inner and outer layers of ischemic tissue did not differ between the two groups, the intensity of ischemia seemed similar. Glycogenolysis was unimpaired in the diabetic ischemic muscle but triglyceride levels remained elevated. Morphologically the diabetic myocardium was characterized by a diffuse accumulation of periodic acid-Schiff-positive glycoprotein in the interstitium, which was thought to limit diastolic filling of the ischemic ventricle and to contribute to the substantial reduction of ventricular performance.
Rate-dependent changes in extracellular potassium in the rabbit atrium.
Authors: Kunze D L
Published: June 2012

We measured levels of potassium ion in the extracellular space of isolated superfused rabbit atria continuously with double-barreled microelectrodes of which on barrel was a K+ liquid ion-exchanger microelectrode and the other a potential-sensing micropipette. Increases in heart rate resulted in transient increases in extracellular potassium ([K+]0). When the quiescent atrium was stimulated the maximal increase was 0.4 mM at rates of 60/min, 0.7 mM at 90/min, 0.9 mM at 120/min, 1.3 mM at 200/min, and 1.8 mM at 300/min. The increase was not sustained during continued stimulation but declined toward prestimulation levels. When the stimulus was terminated the extracellular potassium activity decreased below bathing solution values by 0.2 mM after 60/min, 0.5 mM after 90/min, 0.7 mM ater 120/min, 0.9 mM after 200/min, and 1.0 mM after 300/min and subsequently returned to a value equal to that of the bathing solution. The magnitude of the decline in extracellular potassium activity during prolonged stimulation was markedly decreased when the bathing solution contained either zero potassium, ouabain, LiCl, or a decreased Po2 such that an elevation in [K+]0 persisted during stimulation. Moreover, the reduction in [K+]0 that followed the cessation of stimulation also was inhibited. These results support a role of the Na-K pump in maintaining extracellular potassium activity during changes in cardiac rate.
Collateral circulation after renal artery occlusion in the rat.
Authors: Siegel M B , Levinsky N G
Published: June 2012

We used angiographic and microsphere methods to evaluate the anatomic and functional features of renal collateral circulation in the rat. By the microsphere method, renal parenchymal blood flow was less than 1% of control 1 hour after occlusion of the main renal artery; 2.8% of control 1-2 weeks after arterial occlusion; and 1% of control 4-9 weeks after occlusion. Radiographic observations during chronic occlusion revealed numerous collateral vessels to the kidney. These vessels readily filled with angiographic contrast medium but the intrarenal circulation did not visualize. We conclude that collateral circulation to renal parenchyma is negligible after acute or chronic occlusion of the main renal artery in the rat. The rich anatomic plexus of collateral vessels has no functional significance and is unable to preserve viability of the parenchyma.
Intrarenal hemodynamics in cross-circulated hypervolemic and isovolemic rats.
Authors: Sonnenberg H , Veress A T , Pearce J W
Published: June 2012

The microsphere technique was used to measure renal blood flow and intrarenal flow distribution in cross-circulated pairs of rats. One rat of each pair was made hypervolemic by infusion of blood (2.3% of body weight), followed by intravenous reinfusion to urine to maintain intravascular expansion. The other rat of each pair, which also was urine-reinfused, was kept isvolemic throughout the experiment. As shown previously, blood infusion resulted in a large diuretic and natriuretic response in the hypervolemic partner, while a smaller but statistically significant response occurred in the isovolemic partner. Total renal blood flow did not change in the expanded rats and fell slightly but not significantly in the nonexpanded ones. Blood volume expansion was associated with a significant shift in microsphere concentration from outer to inner cortex. This shift was not, however, correlated with the magnitude of the renal response. The transferred natriuresis in isovolemic partners was not associated with any change in microsphere distribution. We conclude therefore, that redistribution of blood flow to the inner cortex, although a feature of intravascular expansion, is not the primary determinant of volume natriuresis. In addition, the natriuretic activity which develops in the blood of hypervolemic rats can reduce sodium reabsorption in isovolemic rats without intrarenal hemodynamic changes.
The effect of norepinephrine on aortic 42K turnover during deoxycorticosterone acetate hypertension and antihypertensive therapy in the rat.
Authors: Jones A W , Sander P D , Kampschmidt D L
Published: June 2012

We studied the effects of norepinephrine on 42K turnover in aorta isolated from rats. The rats were given saline to drink and were made hypertensive by injections of deoxycorticosterone acetate (DOC). Other groups of rats received in addition either 6-hydroxydopamine (6-OH-DA) or a regimen of antihypertensives (Anti-Hy) consisting of reserpine, hydrochlorothiazide, and hydralazine. The weight, length, wall thickness, and circumference of the aorta also were measured. DOC hypertension was associated with increased 42K turnover (rate constant for DOC = 0.0164 +/- 0.0009 vs. 0.0090 +/- 0.0002 min-1 in controls). The responses of 42K turnover to low doses of norepinephrine (NE) were increased in DOC with an ED50 of 3.5 +/- 0.8 X 10(-9) vs. 2.7 +/- 0.5 X 10(-8) M in controls. The aortic weight, weight/length, and wall thickness were also increased. Rats treated with DOC plus 6-OH-DA had lower blood pressure and smaller changes in aortic dimensions; however 42K turnover and response to NE were similar to those of the DOC group. The Anti-Hv group exhibited only small increase in 42K turnover and aortic dimensions when compared to controls. It is concluded that DOC hypertension is associated with increased response of 42K turnover to NE which in turn may contribute to increased responses reported for contraction. The Anti-Hy regimen was more effective than 6-OH-DA in reducing the increased 42K turnover and response to NE associated with DOC hypertension.
Effect of angiotensin-converting enzyme inhibitor (SQ 20881) on the plasma concentration of angiotensin I, angiotensin II, and arginine vasopressin in the dog during hemorrhagic shock.
Authors: Morton J J , Semple P F , Ledingham I M , Stuart B , Tehrani M A , Garcia A R , McGarrity G
Published: June 2012

The effect of an angiotensin-converting enzyme inhibitor on the circulating levels of angiotensin I, angiotensin II, and arginine vasopressin was studied in dogs subjected to hypotensive hemorrhagic shock. In dogs subjected to hemorrhage but not given the inhibitor, angiotensin II rose 20-fold (from 69 to 1,343 pg/ml of plasma), whereas in dogs subjected to hemorrhage but pretreated with the inhibitor, angiotensin II rose only 2-fold (from 92 to 171 pg/ml of plasma). In the pretreated dogs angiotensin I rose 30-fold (from 108 to 3,232 pg/ml of plasma). There was no statistically significant difference between the vasopressin levels found in the untreated dogs and the levels found in dogs given the inhibitor (1,016 and 1,095 pg/ml of plasma). Of the 15 dogs in the untreated group, five died before retransfusion was completed (four of cardiac failure and one of cardiac arrhythmia); none of the 10 dogs in the inhibitor-treated group died. These observations suggest that the very high levels of angiotensin II observed following severe hemorrhage do not contribute significantly to the increased secretion of vasopressin and that the inhibitor protects against death, possibly by suppressing the very high blood levels of angiotensin II observed following this type of experimental hemorrhagic shock.
Purification of human angiotensinogen.
Authors: Tewksbury D A , Premeau M R , Dumas M L , Frome W L
Published: June 2012

A four-step method for the purification of human angiotensinogen has been devised. The four steps are: (1) removal of albumin by affinity chromatography on blue dextran-Sepharose, (2) chromatography on DEAE-Sephadex, (3) chromatography on hydroxylapatite, and (4) chromatography on DEAE-cellulose. This method is capable of producing 8 mg of purified angiotensinogen from 150 ml of plasma with 33% overall recovery of renin-releasable angiotensin I. The angiotensinogen appears homogeneous by immunochemical and ultracentrifugal techniques. The N-terminal amino acids have been determined to be alanine and aspartic acid or asparagine.
A direct radioimmunoassay for human renin substrate and identification of multiple substrate types in plasma.
Authors: Eggena P , Barrett J D , Hidaka H , Chu C L , Thananopavarn C , Golub M S , Sambhi M P
Published: June 2012

Plasma renin substrate, a widely measured parameter of the renin reaction, is quantitated indirectly by the measurement of liberated angiotensin I upon exhaustive incubation of plasma with added renin. To overcome methodological problems of this assay system, we have developed a direct radioimmunoassay for this plasma protein using renin substrate purified from pooled plasma of normotensive subjects as the antigen. Comparison of substrate quantitated by the two assay systems (direct and indirect) indicates a 1:1 correlation with the exception of certain subjects with elevated substrate levels induced by estrogen therapy. To study the possibility of multiple substrate forms, we have made a comparison of substrate quantitated by both radioimmunoassays in conjunction with electrophoresis of plasma on polyacrylamide gel. One major form of substrate with a retardation factor (Rf) = 0.60 was found in normotensive and essential hypertensive subjects which gave a 1:1 correspondence on quantitation by the two methods. In contrast, six of 16 women on oral contraceptives demonstrated three forms of substrate (Rf = 0.16, 0.35, and 0.60) on electrophoresis. Substrate with Rf = 0.16 and 0.35 did not cross-react with the antiserum prepared against substrate from normotensive subjects, implying structural differences in these proteins.
Partial purification of human renin.
Authors: Murakami K , Inagami T , Haas E
Published: June 2012

An affinity gel for the purification of renin was prepared by coupling pepstatin to aminohexylagarose gel. Partially purified human renin (Haas et al., Arch. Biochem. Biophys., 110, 534-543, 1965) was purified further by affinity chromatography on the pepstatin-aminohexyl-agarose gel, gel filtration on a Sephadex G-75 column, and ion exchange chromatography on a DEAE-cellulose column. Separation from a protease permitted further purification without progressive loss of activity. Three peaks of enzymatically active renin were obtained after the DEAE-cellulose chromatography, with specific activities ranging from 206 to 166 and 85 Goldblatt units/mg protein, respectively. The specific activity of 206 GU units/mg represents a 103,000-fold purification compared to the renin present in the first crude extract.
Hormonal control of plasma renin substrate; (angiotensinogen).
Authors: Krakoff L R , Eisenfeld A J
Published: June 2012

The effect of ethinyl estradiol (EE2) and dexamethasone (Dex) upon plasma renin substrate (PRS) was studied in rats in relation to sexual maturation and pituitary function. Normal adult rats had large increases in PRS when given either EE2 or Dex. Prepubescent (25-day-old) rats also had a substantial increase in PRS following Dex, but no increase in PRS after EE2. In adult rats, hypophysectomy prevented the rise in PRS due to EE2 but did not prevent the increase in PRS due to Dex. Hepatic estrogen and glucocorticoid receptors were measured in immature and adult rats. Immature rats had markedly reduced concentration of hepatic estrogen receptors (16%), compared with adults. In contrast, glucocorticoid receptor concentration was not significantly different between immature and adult rats. The results indicate that the effect of estrogens and glucocorticoids upon PRS are mediated by pathways that are separable at the hormone receptor level.
Inhibition of the in vitro renin reaction by circulating neutral lipids.
Authors: Kotchen T A , Talwalkar R T , Welch W J
Published: June 2012

We have previously reported that the addition of plasma from normotensive human subjects to renin-renin substrate inhibits the in vitro rate of angiotensin generation. The purpose of the present study was to determine whether a renin-inhibiting factor could be identified in human plasma. Neutral lipids and phospholipids were extracted from plasma of seven normotensive control subjects. During 30-, 60-, and 180-minute incubations, neutral lipids inhibited the reaction between human renin and homologous renin substrate (P less than 0.01). Phospholipids did not affect the rate of angiotensin generation (P less than 0.05). The neutral lipid extract was further separated on silica gel chromatographic plates, and several fractions inhibited renin (P less than 0.01) Addition of each of six synthetic neutral lipids to renin-renin substrate did not affect the rate of angiotensin generation. In conclusion, several neutral lipid fractions extracted from human plasma inhibit the in vitro renin reaction.
Detection and localization of multiple epicardial electrical generators by a two-dipole ranging technique.
Authors: Mirvis D M , Keller F W , Ideker R E , Cox J W , Dowdie R F , Zettergren D G
Published: June 2012

The ability of a numerical procedure to detect and to localize two experimentally induced, epicardial dipolar generators was tested in 24 isolated, perfused rabbit heart preparations, suspended in an electrolyte-filled spherical tank. Electrocardiograms were recorded from 32 electrodes on the surface of the test chamber before and after placement of each of two epicardial burns. The second lesion was located either 180 degrees, 90 degrees, or 45 degrees from the first. Signals were processed by iterative routines that computed the location of one or two independent dipoles that best reconstruced the observed surface potentials. The computed single dipole acounting for 99.68% of root mean sequare (RMS) surface potential recorded after the first burn was located 0.26 +/- 0.10 cm from the centroid of the lesion. Potentials recorded after the second lesions were fit with two dipoles that accounted for 99.36 +/- 1.51% of RMS surface potentials and that were located 0.42 +/- 0.26 cm and 0.57 +/- 0.49 cm from the centers of the corresponding burn. Seventy-one percent of computed dipoles were located within the visible perimeter of the burn. Thus, two simultaneously active dipolar sources can be detected and accurately localized by rigorous study of the generated electrical field.
Relationship between acetylstrophanthidin-induced aftercontractions and the strength of contraction of canine ventricular myocardium.
Authors: Ferrier G R
Published: June 2012

Contractile activity was recorded from isolated canine ventricular muscle exposed to acetylstrophanthidin (AS), 0.5 to 2 X 10(-7) g/ml. Development of the positive inotropic effect of AS was accompanied by the appearance of aftercontractions (AC) coupled to the driven responses. The amplitudes of AC increased with the number of preceding beats. Test beats occurring during the ascending limb of AC were potentiated and the potentiation increased with the amplitude of the AC. Beats falling during the descending limb decreased in strength as the amplitude of the AC increased. As eliminated the frequency dependence of restitution. However, staircase phenomena persisted and were then found to be dependent on the phase relationship of each beat to underlying AC. These findings suggest an important role for AC in the inotropic actions of digitalis and in determining strengh-interval relationships of ventricular muscle treated with digitalis.
Effects of acute, passive hepatic congestion on blood flow and oxygen uptake in the intact liver of the cat.
Authors: Lautt W W
Published: June 2012

Raising the hepatic venous pressure experimentally duplicates the type of hepatic congestion seen in many clinical situations including congestive heart failure. Venous pressure was controlled using a hepatic venous long circuit preparation and was raised by 6 cm blood (4.7 mm Hg) or 10 cm (7.8 mm Hg). Total splanchnic blood flow and oxygen uptake were reduced by these maneuvers but hepatic arterial flow was not altered nor was hepatic oxygen uptake. Blood flow in the portal vein decreased to 65 +/- 12% of control and gut oxygen uptake decreased to 60 +/- 14% of control. The data confirm that raised hepatic venous pressure does not produce hepatic edema in spite of massive prolonged fluid filtration across the liver into the peritoneum. In spite of a reduced (to 84 +/- 3% of control) hepatic oxygen delivery, the liver can maintain oxygen uptake (99 +/- 7% of control) by increasing oxygen extraction to appropriate levels. The hepatic artery in these cats were capable of myogenic vasoconstriction in response to altered arterial pressure, but in response to raised venous pressure no tendency for constriction was seen. This is in marked contrast to the vasoconstriction seen in isolated perfused livers where portal blood flow is held constant during the raised venous pressure.
Plasma vasopressin concentrations and effects of vasopressin antiserum on blood pressure in rats with malignant two-kidney Goldblatt hypertension.
Authors: Möhring J , Möhring B , Petri M , Haack D
Published: June 2012

Male Sprague-Dawley rats with unilateral renal artery stenosis and a contralateral untouched kidney develop a malignant hypertension (MH) which is characterized by high blood pressures, sodium and water depletion, and subsequent activation of the renin-angiotensin system. In the present studies we found plasma arginine vasopressin (AVP) concentrations-3-fold higher than those in rats with benign renal hypertension, and 4- to 5-fold higher than those in normotensive control rats. Analysis of individual values showed considerable scatter; about 50% of the values fell in the range of benign hypertensive or control rats. When a specific AVP antiserum was injected, iv, into eight conscious unrestrained MH rats, BP transiently fell toward control values in four; in one, BP fell by only 10 mm Hg, and three other MH rats showed no response. In the same rats, injection of a specific angiotensin II antiserum always induced a transient fall in BP. On the basis of these and previously reported observations, we conclude that, subsequent to sodium and water loss and activation of the renin-angiotensin system, vasopressin release is stimulated in a significant number of MH rats and that, in these rats, vasopressin may cause significant systemic vasoconstriction. Thereby vasopressin may contribute to the development of malignant renal hypertension in rats.
Gas exchange after pulmonary thromboemoblization in dogs.
Authors: Dantzker D R , Wagner P D , Tornabene V W , Alazraki N P , West J B
Published: June 2012

Gas exchange following experimental pulmonary thromboembolization was studied with an inert gas elimination technique in 17 dogs. Pulmonary arterial, systemic arterial, and expired gas concentrations of six gases infused intravenously were measured before embolization and 5, 10, 15, 30, 60, and 120 minutes after embolization. Distributions of ventilation-perfusion (VA/Q) ratios were derived from the measured concentrations. In all dogs, embolization caused an increase in blood flow and ventilation to VA/Q ratios less than 1. There were no lung units with VA/Q ratios between 10 and 100 before embolization, but, in two-thirds of the dogs, such regions developed after embolization. Ventilation to unperfused lung showed a transient increase of 2-6%. Radioisotope studies of lobes removed post-mortem indicated that thromboemboli rarely caused complete abolition of lobar blood flow. Pulmonary embolization did not cause arteriovenous shunts to appear. The hypoxemia caused by embolization could be accounted for by the changes in VA/Q distributions. Over the 2-hour period after embolization, lung function improved as the distributions partially returned toward the preembolization patterns.
Diameter of afferent arterioles during autoregulation estimated from microsphere data in the dog kidney.
Authors: Mørkrid L , Ofstad J , Willassen Y
Published: June 2012

Afferent arteiolar diameters, relative flow distribution, and flow conductance factors are estimated by nonlinear regression analysis of the sieving effect on microspheres in different vascular structures of the dog renal cortex. The data presented are from experiments in which microspheres of 10-30 microgram were injected into the abdominal aorta during normotension and after lowering the blood pressure to the lower limit of autoregulation. Microscopic examination of the spheres trapped in the glomeruli and the renal arteries showed an increasing exclusion of microspheres greater than 15 micrometer from the afferent arterioles during normotension. This effect was most pronounced for the deeper cortical layers and can be explained mainly as geometrical exclusion of spheres from afferent arterioles. During hypotension, progressively larger microspheres entered glomeruli and afferent arterioles, presumably due to vasodilation of the vessels. There was a significant redistribution of microspheres larger than 15 micrometer from the outer to the inner cortex during hypotension without a corresponding redistribution of smaller spheres or the estimated blood flow. Approximately the same degree of dilation of afferent arterioles was observed during autoregulatory hypotension in three cortical layers.
Failure of left atrial distension to alter renal function in the nonhuman primate.
Authors: Gilmore J P , Zucker I H
Published: June 2012

Experiments were undertaken to determine the influence of increasing left atrial pressure on renal function in the nonhuman primate. Significant elevations of left atrial pressure, produced by using an intra-atrial balloon, had no effect on salt or water excretion, renal plasma flow, or glomerular filtration rate. There were no significant changes in heart rate or blood pressure. We conclude that, unlike those in the dog, atrial receptors in the nonhuman primate play little or no role in modulating salt and water excretion.
Clonal markers in the study of the origin and growth of human atherosclerotic lesions.
Authors: Pearson T A , Dillman J M , Solex K , Heptinstall R H
Published: June 2012

The X-linked enzyme, glucose-6-phosphate dehydrogenase (G-6-PD) was used as a cellular marker to study the clonal characteristics of human atherosclerotic lesions from females heterozygous for G-6-PD isoenzymes. Portions of uninvolved aortic wall contained both isoenzyme types (A and B), and their isoenzyme patterns were used to establish criteria for polyclonal lesions. Portions of uterine leiomyomas contained predominantly one isoenzyme type (either all A or all B) and their isoenzyme patterns were used to establish criteria for monoclonal lesions. These techniques were used to address three questions concerning atherogenesis. First, evidence for the monoclonal origin of fibrous-capped plaques was provided by the findings that small plaques had G-6-PD isoenzyme distributions similar to those of leimyomas; that in large plaques with multiple portions assayed for G-6-PD, a large proportion (25 of 26, 96%) of plaques had monoclonal characteristics; and that multiple monoclonal portions were present in the same plaque. Second, the role of the fatty streak as a precursor of fibrous plaques was supported by the demonstration that a proportion (11 of 66, 16.7%) of fatty streaks contained isoenzyme patterns intermediate between those of polyclonal uninvolved aortic wall and monoclonal leiomyomas. Increased cellularity of fatty streaks correlated with increased deviation of isoenzyme pattern toward monoclonality. Third, the assay of portions of both small and large plaques provided no evidence for clonal selection as plaques increase in size.
Morphological changes in isolated perfused dog lungs after acute hydrostatic edema.
Authors: DeFouw D O , Berendsen P B
Published: June 2012

Morphometric data from stable (nonedematous) isolated dog lungs, perfused with nearly cell-free perfusates, were compared to similar stereological evaluations of isolated dog lungs after induction of severe acute hydrostatic edema. In the edematous lungs, capillary surface and volume densities were substantially increased. Alveolar surface density was also increased. Thicknesses of the endothelial and type I epithelial cellular compartments of the air-blood barrier were unchanged. Thickness of the interstitial compartmemt of the air-blood barrier was substantially increased and this, in turn, caused an overall increase in mean thickness of the barrier. Volume densities of the nonparenchymal connective tissue spaces surrounding the extra-alveolar vessels and airways were also increased. In both the endothelial and type I epithelial cells cytoplasmic volume densities of pinocytotic vesicles were increased. In addition, the number of vesicles opening onto the luminal and albuminal cellular surfaces increased signficantly. Transendothelial vesicular passage may contribute to interstitial edema formation, and transepithelial vesicular transport may contribute to alveolar flooding in isolated perfused dog lungs.
Blood pressure and vascular resistance in genetically hypertensive rats treated at birth with 6-hydroxydopamine.
Authors: Clark D W , Jones D R , Phelan E L , Devine C E
Published: June 2012

Genetically hypertensive (GH) rats of the New Zealand strain and normotensive (N) rats were sympathectomized from birth with 6-hydroxydopamine (100 mg/kg,s.c, on alternate days, seven treatments). In adult treated rats from each strain (GHTr and NTr), blood pressure was lower than normal. Functional tests and electron microscopy showed that denervation was virtually complete in mesenteric and hindlimb arteries; the innervation of the renal artery was little affected. Ganglionic blockade still caused a large fall in blood pressure in treated rats. Vascular resistance was higher in blood-perfused hindlimbs and tails of GH rats than in those of N rats; in contrast, resistance was similar in limbs and tails of GHTr and NTr rats and was greater than that found in untreated N rats. Saline-perfused limb vessels had neither neurogenic nor myogenic tone and resistance was higher in GH limbs (whether these were from treated rats or not) than in untreated N limbs. In saline-perfused NTr limbs, there was a paradoxical structural adaptation (probably luminal narrowing) of the hindlimb blood vessels and resistance was higher than in untreated N rats. The resistance of saline-perfused GH and GHTr limbs was similar. A high peripheral resistance appears to be the main mechanism sustaining genetic hypertension, and the integrity of the vasomotor sympathetic nerves is necessary for the development of this form of experimental hypertension.
A comparison of the effects of 5- and 6-hydroxydopamine on the isolated canine saphenous vein.
Authors: Goldberg M R , Kadowitz P J
Published: June 2012

We studied and compared the effects of 5- and 6-hydroxydopamine (5- or 6-OHDA) on venous tone and on adrenergic and nonadrenergic responses of the isolated canine saphenous vein. In the tissue bath, both 5- and 6-OHDA caused increases in tone and abolished adrenergic responses to transmural nerve stimulation. Effects of 6-OHDA were blocked by desmethylimipramine. 6-OHDA reduced norepinephrine levels of venous strips to 15% of those in control strips. Neither 5- nor 6-OHDA markedly altered peak contractile responses to norepinephrine but 6-OHDA prolonged the response to norepinephrine. Both compounds reduced responses to tyramine, with 6-OHDA producing a greater reduction than 5-OHDA. Large contractile responses to 5-OHDA were blocked only partially by treatment of strips with 6-OHDA, suggesting that contractile responses to 5-OHDA were mediated by direct and indirect actions. These results suggest differences in the actions of 5- and 6-OHDA on adrenergic terminals and smooth muscle in saphenous veins. The results of the experiments suggest that both 5- and 6-OHDA may be useful pharmacological interventions for the study of adrenergic mechanisms in isolated blood vessels.
The effects of agents that bind to cytochrome P-450 on hypoxic pulmonary vasoconstriction.
Authors: Sylvester J T , McGowan C
Published: June 2012

The relationship between pulmonary arterial pressure (Ppa) and blood (Q) was determined during normoxia and hypoxia in ventilated pig lungs perfused in situ with the animal's own blood. Hypoxia shifted the Ppa-Q relationship to the right and decreased its slope, indicating pulmonary vasoconstriction. Carbon monoxide (11.5% in the inspired gas) and metyrapone ditartrate (10 mg/min into the perfusate) caused vasodilation when oxygenation was normal and reduced the vasoconstriction caused by hypoxia. Since the only pharmacological property CO and metyrapone are thought to have in common at the concentrations employed is the ability to bind to the heme iron of cytochrome P-450, these results are consistent with the hypothesis that desaturation of this cytochrome leads to pulmonary vasoconstriction. Prostaglandin F2alpha, infused into the pulmonary artery at 0.01 mg/min, when oxygenation was normal, had effects on the Ppa-Q relationship similar to those of hypoxia. The F2alpha response was also reduced by CO and metyrapone, suggesting either that P-450 was involved in the F2alpha response or that CO and metyrapone were toxic to pulmonary vascular smooth muscle. Proadifen hydrochloride (1 mg/min), which is thought to bind to the protein moiety of P-450 also reduced the hypoxic response, but was a vasoconstrictor during normoxia and did not affect the F2alpha response.
Pressor responses to norepinephrine in rabbits with 3-day and 30-day renal artery stenosis. The role of angiotensin II.
Authors: Ichikawa S , Johnson J A , Fowler W L , Payne C G , Kurz K , Keitzer W F
Published: June 2012

Pressor responses to norepinephrine (NE) infusions were examined in normal rabbits, in rabbits with renal artery stenosis of over 30 days' duration (chronic renal hypertensive rabbits), and in rabbits with renal artery stenosis of 3 days' duration (3-day clipped rabbits). The 3-day clipped rabbits did not have hypertension, but they showed the same increased pressor responses to NE as did the chronic renal hypertensive rabbits, which was about 2.5 times that of the normal rabbits. Plasma renin activity (PRA) was the same in the 3-day clipped rabbits as in the normal group, but in the chronic renal hypertensive rabbits the PRA was significantly below normal. Infusions of angiotensin II (A II) in either subpressor or pressor amounts potentiated the pressor responses to NE in normal rabbits, whereas, in 3-day clipped rabbits and chronic renal hypertensive rabbits, A II in subpressor or pressor doses did not alter the pressor responses to NE. Infusion of the A II antagonist, [1-sarcosine, 8-isoleucine]angiotensin II, did not alter the pressor responses of normal rabbits to NE, but this A II analogue completely abolished the pressor hyperresponsiveness to NE in the 3-day clipped rabbits and greatly reduced the NE hyperresponsiveness in the chronic renal hypertensive rabbits; this A II antagonist did not alter the control arterial pressure in any of the three groups of rabbits. These studies show that the increased pressor response to NE in rabbits with renal artery stenosis occurs before the onset of hypertension and thus is not merely a result of the hypertension. Also, these results provide evidence that A II plays an important role in the increased pressor responses to NE in hypertensive and prehypertensive rabbits.
Contribution of systemic venous hypertension to the development of pulmonary edema in dogs.
Authors: Miller W C , Simi W W , Rice D L
Published: June 2012

Systemic venous hypertension (SVH) is a frequent finding in pulmonary edema. To study the possible contributory or even causal role of SVH in pulmonary edema, a dog model was developed in which balloon catheters were placed in the left and right atria. Inflation of the left atrial balloon produced a tendency to pulmonary edema by causing pulmonary venous hypertension (PVH) (pulmonary artery wedge pressure of 20 mmHg). Inflation of the right atrial balloon produced SVH (central venous pressure of 15 mm Hg). After 2 hours, dogs with SVH with or without PVH demonstrated a greater amount of lung fluid accumulation (P less than 0.01) compared to controls or PVH alone. There was no significant difference in lung water in SVH dogs with or without PVH. Pulmonary blood flow was not significantly different between the experimental groups, each of which was less than control. Impairment of pulmonary lymphatic flow is one possible mechanism producing the worsening edema; however, bronchial venous hypertension or neurogenic reflexes cannot be excluded. We conclude that the contribution of systemic venous hypertension to the development of pulmonary edema may have therapeutic implications.
Alpha-adrenergic receptors in rat myocardium. Identification by binding of [3H]dihydroergocryptine.
Authors: Williams R S , Lefkowitz R J
Published: June 2012

[3H]Dihydroergocryptine ([3H]DHE) binds to sites in membranes derived from rat myocardium that have the characteristics expected of alpha-adrenergic receptors. The binding is saturable with 41 fmol [3H]DHE bound per mg of protein and of high affinity with KD = 2.9 nM. The binding is rapid and readily reversible. Adrenergic agonists compete with [3H]DHE for binding in the order: epinephrine greater than norepinephrine greater than isoproterenol; and adrenergic antagonists compete for binding in the order: phentolamine greater than propranolol. For comparison, (-)[3H]dihydroalprenolol [(-)[3h]dha] was used to bind to sites in the same membrane preparations having characteristics of beta-receptors. The number and affinity of beta-receptors were quite similar to those of the alpha-receptors with 46 fmol (-)[EH]DHA per mg protein bound at saturation and KD = 2.5 nM. These techniques allowed identification of both beta- and alpha-adrenergic receptors in membranes derived from isolated atria, right ventricular free walls, and left ventricles including interventricular septa. This is the first report documenting direct identification of myocardial alpha-receptors by radioligand-binding techniques and complements the literature previously reporting myocardial inotopic and electrophysiological responses to alpha-adrenergic stimulation.
Effects of acetylcholine on the ventricular specialized conducting system of neonatal and adult dogs.
Authors: Danilo P , Rosen M R , Hordof A J
Published: June 2012

We determined the effects of acetylcholine on automaticity of isolated cardiac Purkinje fibers from neonatal and adult dogs and on the idioventricular rhythm of adult dogs with complete atrioventricular block. Isolated Purkinje fibers were studied with standard microelectrode techniques during superfusion with Tyrode's solution at 37 degrees C. For both age groups, spontaneous rate was decreased by acetylcholine, an effect which was reduced by atropine. The magnitude of the effect is equal in both neonatal and adult dogs. The negative chronotropic effect of acetylcholine was not prevented by phentolamine, indicating that an alpha-adrenergic mechanism was not involved. The idioventricular rate of conscious dogs with formalin-induced heart block was decreased by administration of acetylcholine. The effect was augmented by propranolol and attenuated by atropine. Thus, for both the in vitro and in situ ventricular specialized conducting system, acetylcholine decreases automaticity presumably through combination with a muscarinic receptor.