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Biomedical subjects

G Christensen

Publications and source records attributed to G Christensen.

At least 91 records · Page 5Linked to original sources
PubMed1992

Importance of nitric oxide in canine femoral circulation: comparison of two NO inhibitors.

OBJECTIVE: The aim was to assess the importance of endothelium derived nitric oxide (NO) in the regulation of vascular tone in the limbs. Changes in the canine femoral circulation were investigated after inhibition of NO synthesis. METHODS: The effects of two NO inhibitors, NG-monomethyl-L-arginine (LNMMA) and NG-nitro-L-arginine (NOARG), were compared on basal femoral blood flow and on endothelium dependent (acetylcholine) and endothelium independent (glyceryl trinitrate) vasodilatation in 15 pentobarbitone anaesthetised mongrel dogs. An electromagnetic flow probe was placed on the femoral artery to measure femoral blood flow. One catheter was advanced into the femoral artery proximal to the flow probe for blood pressure recording and another catheter distal to the flow probe for drug infusions. RESULTS: LNMMA (0.28 mumol.ml-1) reduced basal femoral blood flow by 44(SEM 3)%, NOARG (0.07 mumol.ml-1) by 21(4)%, and NOARG (0.56 mumol.ml-1) by 29(3)%. The flow responses to acetylcholine were reduced after LNMMA by 27(8)%, unaltered after NOARG (0.07 mumol.ml-1), and reduced after NOARG (0.56 mumol.ml-1) by 60(7)%. The flow response to glyceryl trinitrate was unaltered. L-arginine re-established femoral blood flow after infusion of LNMMA and NOARG (0.07 mumol.ml-1), but L-arginine did not re-establish femoral blood flow after NOARG (0.56 mumol.ml-1), even when infused in a 60-fold molar excess. CONCLUSIONS: There is a continuous basal release of NO in the canine femoral circulation. The results obtained by infusing LNMMA suggest that more than 40% of basal femoral blood flow is mediated by endothelium derived NO. Whereas LNMMA was more potent than NOARG in reducing basal NO release, NOARG (0.56 mumol.ml-1) reduced acetylcholine induced vasodilatation by as much as 60%.

Acetylcholine↗
PubMed1992

Effect of atrial natriuretic factor on renal prostaglandin E2 release in the anaesthetized dog.

Experiments were undertaken in two groups of barbiturate anaesthetized dogs to examine whether atrial natriuretic factor (ANF) exerts an effect on renal release of prostaglandin E2 (PGE2). In the first group, intravenous infusion of ANF (50 ng min-1 kg-1 body wt) reduced basal PGE2 release from 4.4 +/- 0.8 pmol min-1 to 1.8 +/- 0.7 pmol min-1. In the second group, intrarenal infusion of an alpha 1-adrenoceptor agonist, phenylephrine (2.5-6.75 micrograms min-1), raised PGE2 release from 2.7 +/- 0.5 pmol min-1 to 7.5 +/- 1.3 pmol min-1. During continuous alpha 1-adrenergic stimulation, intravenous infusion of ANF (100 ng min-1 kg-1 body wt) reduced PGE2 release to 3.5 +/- 1.0 pmol min-1. These results demonstrate that ANF reduces basal and alpha 1-adrenergic stimulated renal PGE2 release.

Adrenergic alpha-Agonists↗
PubMed1992

Characteristics and development of myocardial stunning in the pig.

Regional left ventricular function associated with consecutive ischemic periods of 2, 2, 5, 10, and 2 min was recorded by ultrasonic technique in pentobarbital-anesthetized pigs. All systolic and diastolic derangements first appeared after 5 min of ischemia, and all worsened after 10 min of ischemia. Percent systolic segment length shortening reached nadirs 23 (17-29)% (P less than 0.001) and 54 (45-65)% (P less than 0.001) below baseline 30 min after 5 and 10 min of ischemia. During reperfusion all recorded systolic and diastolic variables transiently recovered and then deteriorated with a closely similar time course. This covariance indicates that systolic and diastolic derangements are causally related, and because diastolic compliance was preserved in stunned myocardium we conclude that all derangements largely result from reduced systolic tension development. Transient postischemic hypercontractility followed all occlusions and was not attenuated by beta-blockade and not mimicked by hyperemia alone. Postischemic hypercontractility was greatly enhanced in stunned myocardium, and we hypothesize that more pronounced and sustained postischemic elevation of intracellular Ca2+ concentration explains this observation.

Adrenergic beta-Antagonists↗
PubMed1992

Inhibition of renal nitric oxide synthesis with NG-monomethyl-L-arginine and NG-nitro-L-arginine.

In barbiturate-anesthetized dogs, the effects of intrarenal infusion of the two selective inhibitors of nitric oxide synthesis, NG-monomethyl-L-arginine (L-NMMA) and NG-nitro-L-arginine (NO-Arg), were compared. Basal renal blood flow (RBF) was reduced by 15 +/- 2% after L-NMMA at 0.28 mumol/ml, by 20 +/- 3% after NO-Arg at 0.07 mumol/ml, and by 31 +/- 5% after NO-Arg at 0.56 mumol/ml. Endothelium-dependent vasodilation induced by intrarenal infusion of acetylcholine was unaltered after L-NMMA, reduced by 24 +/- 3% after NO-Arg at 0.07 mumol/ml, and reduced by 59 +/- 13% after NO-Arg at 0.56 mumol/ml. Endothelium-independent vasodilation induced by intrarenal infusion of atrial natriuretic factor was not reduced after L-NMMA and NO-Arg. This study shows that NO-Arg is more potent than L-NMMA in inhibiting basal renal nitric oxide synthesis. In contrast to L-NMMA, NO-Arg exerted an inhibitory effect on acetylcholine-induced renal vasodilation. Our findings indicate that one-third of the basal RBF and more than one-half of the increase in RBF during acetylcholine infusion are dependent on nitric oxide synthesis.

Acetylcholine↗
PubMed1992

Atrial natriuretic factor and renal sodium excretion during ventilation with PEEP in hypervolemic dogs.

Controlled mandatory ventilation with positive end-expiratory pressure (PEEP) reduces renal sodium excretion. To examine whether atrial natriuretic factor (ANF) is involved in the renal response to alterations in end-expiratory pressure in hypervolemic dogs, experiments were performed on anesthetized dogs with increased blood volume. Changing from PEEP to zero end-expiratory pressure (ZEEP) increased sodium excretion by 145 +/- 61 from 310 +/- 61 mumol/min and increased plasma immunoreactive (ir) ANF by 104 +/- 27 from 136 +/- 21 pg/ml. Changing from ZEEP to PEEP reduced sodium excretion by 136 +/- 36 mumol/min and reduced plasma irANF by 98 +/- 22 pg/ml. To examine a possible causal relationship, ANF (6 ng.min-1.kg body wt-1) was infused intravenously during PEEP to raise plasma irANF to the same level as during ZEEP. Sodium excretion increased by 80 +/- 36 from 290 +/- 78 mumol/min as plasma irANF increased by 96 +/- 28 from 148 +/- 28 pg/ml. We conclude that alterations in end-expiratory pressure lead to great changes in plasma irANF and sodium excretion in dogs with increased blood volume. Comparison of the effects of altering end-expiratory pressure and infusing ANF indicates that a substantial part of the changes in sodium excretion during variations in end-expiratory pressure can be attributed to changes in plasma irANF.

Animals↗
PubMed1991

Renal uptake and degradation of trapped-label calcitonin.

In order to quantitate the role of the kidneys in the clearance and degradation of calcitonin, a trapped-label procedure was used to label human calcitonin. In contrast to conventional [125I]calcitonin, the trapped-label preparation allows quantitative measurements of the extent of uptake as well as of degradation in vivo because the final degradation products do not leave the cells. Trapped-label calcitonin activated adenylate cyclase of bone cells and kidney, as did the native hormone. Ten minutes after intravenous injection into rats, 16% of a trace dose was found in the kidneys. Renal recovery increased to 20% after one hour; in addition, 14% of the injected dose was found in the urine. Eighty per cent of the radioactivity in the urine was in high-molecular weight material. After 90 min, the sum of the accumulated radioactivities in the kidneys and the urine reached 40% of the dose. More than 80% of the radioactivity was sedimentable by centrifuging in a density gradient, indicating that intact calcitonin, as well as the degradation products in the cells, were enclosed within membrane-bound vesicles. Two minutes after injection of trapped-label calcitonin, the peak of radioactivity was found in light gradient fractions associated with cell membrane marker enzymes. Between 5 and 15 min, the peak migrated from light fractions to heavy fractions containing lysosomal marker enzymes. After just 2.5 min, 61% of the renal radioactivity was in low-molecular weight degradation products, as determined by gel filtration. The kinetics of renal degradation of calcitonin indicate that substantial amounts of endocytosed calcitonin is degraded before the hormone reaches the lysosomes.

Adenylyl Cyclases↗
PubMed1991

Atrial natriuretic factor reduces renin release by opposing alpha-adrenoceptor activity.

To examine how atrial natriuretic factor (ANF) inhibits renin release during renal sympathetic nerve stimulation, experiments were performed in barbiturate-anesthetized dogs. In five dogs, intravenous ANF infusion (50 ng.min-1.kg body wt-1) reduced renin release induced by renal nerve stimulation (1 Hz) from 16.8 +/- 8.4 to 3.5 +/- 2.1 micrograms angiotensin I (ANG I)/min. In two groups, renin release was raised by ureteral occlusion, which enhances the effects of beta-adrenoceptor stimulation and increased prostaglandin synthesis. During ureteral occlusion, intrarenal infusion of isoproterenol (0.2 micrograms.min-1.kg body wt-1) increased renin release in eight dogs to 82.6 +/- 10.9 micrograms ANG I/min, which was not significantly reduced by ANF infusion (81.1 +/- 10.1 micrograms ANG I/min). Similarly, intrarenal infusion of arachidonic acid (80 micrograms.min-1.kg body wt-1) during ureteral occlusion increased renin release in five dogs to 22.2 +/- 3.0 micrograms ANG I/min, which was not significantly reduced by ANF infusion (22.5 +/- 3.5 micrograms ANG I/min). Finally, in six dogs examined at free urine flow, intrarenal infusion of phenylephrine, an alpha-adrenergic agonist, raised renin release from 0.5 +/- 0.3 to 20.1 +/- 6.8 micrograms ANG I/min, which was reduced to 10.6 +/- 3.9 micrograms ANG I/min by intravenous ANF infusion (100 ng.min-1.kg body wt-1). These results indicate that ANF does not counteract stimulation of renin release by beta-adrenoceptors and prostaglandins but reduces nerve-stimulated renin release by opposing alpha-adrenoceptor activity.

Adrenergic alpha-Antagonists↗
PubMed1991

Right and left atrial diameters during incremental atrial pacing in pigs.

The relationship between right and left atrial diameters and heart rate was examined in 14 open-chest barbiturate-anesthetized pigs by an ultrasonic technique. The maximal atrial diameter was read at the top of the v wave, which decreased in both atria when heart rate was increased from 124 (118-130) to 159 (156-160) (median and 95% confidence interval) beats/min. Right and left atrial maximal diameter fell significantly from 25.7 (23.6-32.6) to 24.9 (22.9-29.5) mm and from 30.8 (25.1-37.2) to 29.8 (23.4-36.3) mm, respectively, when heart rate was increased from 124 to 180 (177-182) beats/min. At higher pacing frequencies, both right and left atrial maximal diameter progressively increased, and at 220 (216-221) beats/min the maximal diameter regained the values obtained at 124 beats/min. The minimal atrial diameter, which was read at the end of the a wave, remained unchanged at heart rates below 180 beats/min but rose significantly at higher rates. Our findings indicate progressively reduced atrial filling with increasing heart rate and hampered atrial emptying and atrial distension at the highest heart rates.

Animals↗
PubMed1991

Release of atrial natriuretic factor during selective cardiac alpha- and beta-adrenergic stimulation, intracoronary Ca2+ infusion, and aortic constriction in pigs.

The effects of alpha- and beta-adrenergic stimulation on release of atrial natriuretic factor (ANF) were examined in seven anesthetized, open-chest pigs. The alpha-adrenergic agonist phenylephrine (28.0 micrograms/min) and the beta-adrenergic agonist isoproterenol (0.3 micrograms/min) were infused into the proximal part of the circumflex coronary artery to stimulate the left atrial adrenoceptors without concomitant changes in left and right atrial filling pressures (v wave). Isoproterenol reduced plasma immunoreactive ANF (irANF) by 15 +/- 7 pg/ml (20%) from 76 +/- 10 pg/ml despite a rise in left atrial systolic pressure (a wave). A comparable rise in left atrial systolic pressure, induced by intracoronary infusion of calcium chloride (8.0 mg/min), increased plasma irANF by 33 +/- 10 pg/ml (53%) from 62 +/- 7 pg/ml. Phenylephrine increased plasma irANF by 9 +/- 4 pg/ml (14%) from 66 +/- 10 pg/ml without altering right and left atrial pressures. A rise in left atrial filling pressure of 3.2 +/- 0.5 mm Hg, induced by constricting the ascending aorta, increased plasma irANF by 83 +/- 35 pg/ml (141%) from 59 +/- 11 pg/ml. This increase was nine times that during phenylephrine infusion. In conclusion, alpha-adrenergic stimulation increases and beta-adrenergic stimulation inhibits ANF release by a direct action on the atrial myocytes. The direct effects of alpha- and beta-adrenergic stimulation on ANF release in vivo are small compared with the effect of a moderate rise in atrial filling pressure.

Animals↗
PubMed1990

Influence of angiotensin on total intravascular capacity in the anaesthetized pig.

The present study examined the influence of angiotensin on total intravascular capacity. In eight anaesthetized pigs, splenectomy, carotid sinus denervation and cervical vagotomy were performed. Blood was drained from the venae cavae to an extracorporeal reservoir and returned to the right atrium at a constant rate so that changes in total intravascular volume could be recorded as the inverse of changes in reservoir volume. Angiotensin administration at 0.2 microgram kg-1 min-1 i.v. for 5 min was associated with a decrease in total intravascular volume of 57 +/- 6 ml (P less than 0.05) and an increase in aortic pressure from 96 +/- 5 to 119 +/- 6 mmHg (P less than 0.05). With subsequent angiotensin administration in five of the animals, the responses were not attenuated. In five of the animals, angiotensin was associated with a decrease in intravascular volume of 72 +/- 8 ml (P less than 0.05) before abdominal evisceration and 33 +/- 13 ml (P less than 0.05) after evisceration. These responses were significantly different from each other. In four of these eviscerated animals, angiotensin was associated with a decrease in intravascular volume of 35 +/- 17 ml (P less than 0.05) before ligation of all four limbs and a decrease of 36 +/- 4 ml (P less than 0.05) after limb ligation. Thus, angiotensin acts directly to decrease total intravascular volume. The decrease is due to decreases in both splanchnic and extrasplanchnic volume. The extrasplanchnic volume decrement is not due to decreases in skeletal muscle or cutaneous tissue intravascular capacity in the limbs.

Angiotensin II↗
PubMed1990

Influence of atrial natriuretic factor on intravascular volume displacement in pigs.

The present study was undertaken to quantitate the influences of transcapillary fluid loss, urine output, and the capacity vessels on volume displacement toward and away from the right heart during atrial natriuretic factor (ANF) administration. In eight anesthetized pigs undergoing carotid denervation, cervical vagotomy, and splenectomy, blood was drained from the venae cavae to an extracorporeal reservoir and returned to the right atrium at a constant rate so that volume displacement toward and away from the heart could be recorded as change in reservoir volume. Human ANF-(99-126) (0.1 micrograms.kg-1.min-1) for 15 min was associated with a decrease in reservoir volume of 2.7 +/- 0.4 ml/kg (P less than 0.05), which resulted from a decrease in total blood volume of 8.6 +/- 1.0 ml/kg (P less than 0.05) and a displacement from the capacitance vasculature of 5.9 +/- 1.3 ml/kg (P less than 0.05). Since urine output increased only slightly, virtually all of the total blood volume decrement was due to a displacement of fluid into the extravascular space. Thus ANF acts to displace volume away from the right heart. The displacement is due almost entirely to an increase in transcapillary fluid loss; however, volume displacement from the capacity vessels to the right heart partially counteracts this transcapillary influence.

Animals↗
PubMed1989

Atrial natriuretic factor induces natriuresis during pacing tachycardia in dogs.

To examine whether release of atrial natriuretic factor (ANF) can explain the increase in sodium excretion during supraventricular tachycardia, we compared the natriuretic responses with right atrial pacing tachycardia and ANF infusion in six barbiturate-anesthetized dogs. When we raised the dogs' heart rates from 148 +/- 12 to 263 +/- 12 beats/min for 30 min, plasma immunoreactive (IR) ANF rose from 42.1 +/- 3.4 to 139.0 +/- 25.6 pg/ml. Sodium excretion increased from 36.2 +/- 12.8 to 132.4 +/- 40.8 mumol/min in the exposed denervated kidney. When we infused 12.5 ng.min-1.kg body wt-1 of ANF at a spontaneous heart rate of 146 +/- 12 beats/min, plasma IR-ANF rose from 46.0 +/- 5.1 to 121.7 +/- 17.5 pg/ml, which was similar to that observed during pacing tachycardia. Sodium excretion increased from 40.6 +/- 11.3 to 193.6 +/- 46.0 mumol/min, which was higher than that observed during pacing tachycardia. Renal blood flow was lower during pacing tachycardia than during ANF infusion, but glomerular filtration rate and aortic blood pressure were not significantly different during the two procedures. Because sodium excretion was 30% lower during pacing tachycardia, even though plasma IR-ANF was as high as during ANF infusion, we conclude that ANF induces the acute rise in sodium excretion during pacing tachycardia but that hemodynamic changes may attenuate the natriuretic response.

Animals↗
PubMed1989

Release of atrial natriuretic factor during infusion of isoproterenol and angiotensin II.

Release of atrial natriuretic factor (ANF) is related to atrial pressure and heart rate and may be influenced by beta-adrenergic stimulation and angiotensin II. Experiments in five closed-chest dogs showed lower plasma immunoreactive (ir) ANF during intravenous (iv) isoproterenol (0.2-0.3 micrograms.kg-1.min-1) and higher plasma ir-ANF during iv angiotensin II (0.2-0.3 micrograms.kg-1.min-1) than during blood volume expansion measured at equal mean right atrial pressure (RAP) and heart rate. This indicated that the agents may affect ANF release differently, possibly through their effects on left atrial pressure (LAP). In five open-chest dogs with right atrial pacing at 216 +/- 1 beats/min, blood volume was expanded until mean RAP was 9 mmHg. Mean LAP rose to 16.8 +/- 2.0 mmHg, and plasma ir-ANF rose from 57 +/- 6 to 219 +/- 39 pg/ml. At a constant mean RAP of 9 mmHg, iv isoproterenol infusion reduced mean LAP to 12.6 +/- 1.4 mmHg and reduced plasma ir-ANF by 115 +/- 31 to 105 +/- 13 pg/ml. During iv angiotensin II infusion at a mean RAP of 9 mmHg, mean LAP rose to 23.2 +/- 2.2 mmHg and plasma ir-ANF averaged 281 +/- 77 pg/ml. The correlation between plasma ir-ANF and LAP (r = 0.83) indicates that the different effects of isoproterenol and angiotensin II on ANF release can be accounted for by the effects on LAP.

Angiotensin II↗
PubMed1988

The release mechanism for atrial natriuretic factor during blood volume expansion and tachycardia in dogs.

Atrial natriuretic factor (ANF) is released during blood volume expansion and tachycardia, but only blood volume expansion causes atrial distension, which presumably promotes ANF release. Our study was undertaken to search for a common release mechanism. In five anaesthetized, closed-chest dogs, plasma immunoreactive (IR) ANF was measured at three levels of blood volume, which were obtained by infusing a Ringer's solution. At each level of blood volume, plasma IR-ANF was measured at three pacing frequencies. Plasma IR-ANF increased as mean right atrial pressure (mRAP) was raised from 2 to 10 mmHg by volume expansion, whereas pacing tachycardia (at heart rates (HR) 50 +/- 3 and 98 +/- 1 beats min-1 above control) at each level of blood volume expansion increased plasma IR-ANF and systolic RAP (sRAP) at constant mRAP. Plasma IR-ANF was more strongly correlated to sRAP (r = 0.83) than to mRAP (r = 0.69), but the product sRAP x HR had the highest correlation coefficient (r = 0.86). According to the multiple regression equation: plasma IR-ANF = k1 + k2mRAP + k3sRAP + k4sRAP x HR, the product sRAP x HR had the highest coefficient of determination (r2 = 0.75) and was the only significant determinant. We conclude that atrial tension or stress, developing during each atrial systole, is an important determinant of ANF release. Since atrial diastolic and systolic dimensions do not increase during pacing tachycardia, ANF release is not dependent on atrial distension.

Animals↗