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PubMed1995

Halothane impairs the hemodynamic influence of endothelium-derived nitric oxide.

BACKGROUND: The endogenous vasodilator endothelium-derived nitric oxide (EDNO) contributes to the regulation of vascular tone and organ perfusion. It has been suggested that some volatile anesthetics may diminish the influence of EDNO and thereby decrease regional blood flow. METHODS: Radioactive microspheres were used to determine regional hemodynamics in rats. The authors tested the hypothesis that halothane inhibits EDNO and, therefore, should diminish the response to nitric oxide synthesis inhibition by NW-nitro-L-arginine methyl ester (L-NAME) compared with either conscious or barbiturate-anesthetized rats. RESULTS: NW-nitro-L-arginine methyl ester decreased blood flow to the brain by 23% (P < 0.005) in conscious rats to a level similar to that seen with either anesthetic agent. In both conscious and barbiturate-anesthetized rats, L-NAME increased blood pressure (BP) by 24 +/- 2 (P < 0.001) and 20 +/- 1 (P < 0.001) mmHg and total peripheral resistance (TPR) by 132% (P < 0.001) and 105% (P < 0.001), respectively. In contrast, during halothane anesthesia, both the pressor response (only 7 +/- 1 mmHg) and the increase in TPR (only 22%) were greatly diminished (P < 0.001). NW-nitro-L-arginine methyl ester decreased cardiac output (CO) by 47% (P < 0.001) and heart rate (HR) by 28% (P < 0.001) in conscious rats. In barbiturate-anesthetized rats, L-NAME decreased CO by 38% (P < 0.005) and HR by 13% (P < 0.001). In halothane-anesthetized rats, L-NAME changed neither CO nor HR. Thus halothane anesthesia largely eliminated the systemic response to EDNO synthesis inhibition. In conscious rats, L-NAME decreased blood flow to the heart (30%) and kidneys (47%). In barbiturate-anesthetized rats, L-NAME did not alter blood flow to the heart but decreased renal blood flow by 35% (P < 0.005). In halothane-anesthetized rats, L-NAME did not alter blood flow to either the heart or the kidneys. Overall, halothane blunted or blocked the systemic and regional hemodynamic responses to EDNO synthesis inhibition seen in conscious and barbiturate-anesthetized rats. CONCLUSIONS: Halothane anesthesia greatly diminished or eliminated all systemic and regional hemodynamic responses to L-NAME. These data indicate that halothane anesthesia inhibits EDNO-mediated regulation of systemic and organ hemodynamics.

Animals↗

PubMed1988

Manipulation of ascitic fluid pressure in cirrhotics to optimize hemodynamic and renal function.

Intra-abdominal pressure (IAP), measured via a transurethral catheter, hemodynamic, and renal functions were evaluated in 25 cirrhotic patients admitted to ICU with variceal bleeding, tense ascites, and peripheral edema. In patients with an IAP greater than 25 cm H2O, a paracentesis was performed to decrease the IAP by 10 cm H2O. After paracentesis, a decrease in the IAP from 33.47 to 19.06 cm H2O (p less than 0.001) resulted in a decrease in total peripheral resistance (TPR) (p less than 0.01) and a significant increase in cardiac index (CI) (p less than 0.001), stroke index (p less than 0.001), left ventricular stroke work (LVSW) (p less than 0.01), and right ventricular stroke work (p less than 0.01). The therapeutic effects of paracentesis on renal function were: a decrease in BUN and serum creatinine (p less than 0.001) and an increase in the creatinine clearance (Ccr) (p less than 0.001), urine volume (p less than 0.001), osmolar clearance (Cosm) (p less than 0.001), and urine creatinine (p less than 0.001) values. The IAP correlated directly with the TPR (r = +0.35, p less than 0.01) and inversely with the CI (r = -0.39, p less than 0.001) and LVSW (r = -0.37, p less than 0.001) in the 126 studies of IAP performed with the 25 patients. IAP also correlated directly with BUN (r = 0.40, p less than 0.001), serum creatinine (r = 0.28, p less than 0.01), and free water clearance (CH2O) (r = 0.3, p less than 0.001); IAP correlated negatively with Ccr (r = -0.54, p less than 0.001) and Cosm (r = -0.43, p less than 0.001). In critically ill cirrhotic patients, IAP, when measured noninvasively via a bladder catheter, is an accurate and useful method to follow manipulation of ascitic fluid pressure quantitatively in order to optimize hemodynamic and renal function.

Abdomen↗

PubMed1999

A novel candidate presenilin-1 interacting protein containing tetratricopeptide repeats.

The yeast two-hybrid system, immunofluorescence and co-immunoprecipitation techniques were used to identify a novel candidate protein with which presenilin-1 (PS-1) interacts. This interacting protein, the gene of which is encoded on chromosome 16, contains two tetratricopeptide repeats (TPR) that are known to mediate interactions between proteins, appears to be primarily localized to the cytoplasm of transfected HEK293 cells, and is expressed in brain. Preliminary yeast two-hybrid data suggests this candidate may interact with both heat shock protein-90 and heat shock protein-70 and thus may be a novel member of TPR-containing proteins which interact with this complex.

Alzheimer Disease↗

PubMed1987

Systemic haemodynamics in renovascular hypertension: changes after revascularization with percutaneous transluminal angioplasty.

The systemic haemodynamic pattern and its changes after at least 6 months of successful percutaneous transluminal angioplasty (PTRA) was evaluated in a group of patients with renovascular hypertension (RVH). Fourteen patients, nine males and five females, aged 21 to 58 years, were studied; 12 had fibrodysplastic and two had atherosclerotic stenosing renal vascular lesions. Seven were cured and seven improved. Hypertension was characterized by increased plasma volume (PV) and total peripheral vascular resistance (TPR). Mean peripheral plasma renin activity (PRA) and 24-h urine aldosterone (UA) were elevated. However, the vasoconstriction did not appear to be related to the increased activity of the renin-angiotensin system. After at least 6 months of a successful PTRA, the fall in blood pressure (BP) was associated with a decrease in TPR; PV appeared normal, and PRA and UA became normal.

Adult↗

PubMedDate not supplied

Characterization of the coronary vasodilator and hemodynamic actions of monensin, a carboxylic ionophore.

The effects of monensin on coronary blood flow (CBF) and other hemodynamic parameters were studied in anesthetized dogs. A dose-response relationship was established, and it was found that the lowest doses of monensin (5-25 micrograms/kg) produced a dose-dependent increase (3-5x) in CBF with a concomitant decrease in total peripheral resistance (TPR). Pretreatment with diphenhydramine, atropine, indomethacin, or propranolol resulted in no reduction in peak increase in CBF or in the duration of response to monensin. However, the response was partially blocked by aminophylline. Large doses (100 and 200 micrograms/kg) produced a dose-dependent increase in cardiac output, aortic pressure, and LV dP/dt max. The duration of these effects was dose-dependent, ranging from 60 to 120 min or longer. Heart rate remained unchanged with all doses of monensin. Pretreatment with propranolol, H87/07 (a cardioselective beta-blocker), and D-600 given alone or in combination significantly reduced, but did not completely abolish, the monensin-induced increase in LV dP/dt max and aortic pressure responses. The increase in CBF in the left anterior descending coronary artery was not significantly affected by these drug pretreatments. Thus, our studies indicate that monensin has two distinct pharmacological effects--in the lower dose range (less than 25 micrograms/kg) it produces a direct relaxation of the blood vessels resulting in an increase in CBF and a decrease in TPR; at high doses (greater than 25 micrograms/kg) it increases myocardial contractility and aortic blood pressure.

Animals↗

PubMedDate not supplied

Antihypertensive effect of propranolol in conscious spontaneously hypertensive rats: central hemodynamics, plasma volume, and renal function during beta-blockade with propranolol.

In order to obtain a better insight into the hemodynamic changes during beta-blockade, we measured central hemodynamics, plasma volume, and renal function during both acute and long-term beta-blockade in conscious spontaneously hypertensive rats (SHR). Acutely, both 1 and 5 mg/kg propranolol immediately decreased heart rate (HR) and cardiac output (CO). However, total peripheral resistance (TPR) rose sharply, thus preventing mean arterial pressure (MAP) from falling during the first hours after injection. After 4 h TPR had returned to control values and, because CO was still reduced, MAP was lowered. This decrease of MAP persisted for more than 20 h. During 5-day infusion of propranolol (5 mg/kg/day) CO fell on the 1st day and remained lowered during the 5-day period. MAP was lowered from the second day onward. Despite the reduced CO and MAP, plasma volume (PV) did not increase during the 5-day infusion. Acute injection of 5 mg/kg/day did, however, result in a decreased PV at 1 h postinjection. In this time span central venous pressure remained unchanged. Quantitation of water and sodium excretion revealed an immediate diuresis and natriuresis after acute administration of propranolol. This occurred despite a reduced glomerular filtration rate and effective renal plasma flow, as quantitated by indicator clearance methods. We conclude that propranolol reduced tubular sodium reabsorption, possibly through blockade of tubular beta-receptors. This effect may be essential for the long-term antihypertensive efficacy of beta-blockers because it prevents sodium and water retention in a state of reduced MAP and CO.

Animals↗

PubMedDate not supplied

Systemic and pulmonary hemodynamic effects of indapamide in patients with mild arterial hypertension.

We studied the hemodynamic mechanism responsible for the antihypertensive effect of indapamide in eight patients with mild essential hypertension. Systemic and pulmonary hemodynamics were measured using direct techniques (right heart catheterization and thermodilution method), before and 7-10 days after oral treatment with indapamide (2.5 mg/day). Indapamide reduced mean arterial blood pressure from 120 +/- 1.6 (mean +/- SE) to 101 +/- 1.4 mm Hg (p less than 0.01), and mean pulmonary artery pressure from 21 +/- 0.59 to 17 +/- 1.05 mm Hg (p less than 0.01). Total peripheral vascular resistance (TPR) and pulmonary vascular resistance were reduced from 36 +/- 0.85 to 29 +/- 0.72 U/m2 (p less than 0.01) and from 4.3 +/- 0.17 to 3.8 +/- 0.18 U/m2 (p less than 0.01), respectively. Indapamide did not change cardiac index (CI) (3,311 +/- 61.6 vs. 3,325 +/- 72.1 ml/min/m2), heart rate (HR) (75 +/- 1.7 vs. 75 +/- 9 beats/min), mean rate of left ventricular ejection index 140 +/- 2.04 vs. 139 +/- 1.99 ml/s/m2, and stroke index (44 +/- 5.6 vs. 43 +/- 5.8 ml/m2). Mean pulmonary wedge pressure decreased from 7 +/- 0.6 to 5 +/- 0.5 mm Hg (p less than 0.05). Body weight, 24-h urinary volume, and hematocrit were unchanged after treatment. We conclude that the hemodynamic mechanism responsible for the antihypertensive action of indapamide is a reduction in TPR without changes in CI and HR.

Adult↗

PubMed1988

Beneficial effects of fenoldopam on systemic and regional hemodynamics in rabbits with congestive heart failure.

Fenoldopam (SKF 82526 J) is a selective DA-1 receptor agonist and thus of a potential benefit for promoting afterload reduction, renal vasodilatation, and diuresis in congestive heart failure. To examine the acute effects of fenoldopam in heart failure, studies were performed in control rabbits (n = 6) and in rabbits with chronic congestive heart failure (CHF, n = 6) induced by adriamycin treatment. Cardiovascular variables and regional blood flows were determined before and after an infusion of fenoldopam (150 micrograms/kg total dose). Resting hemodynamics differed in CHF and control groups. In the CHF group, mean arterial pressure (MAP), cardiac output (CO), and stroke volume (SV) were reduced and right atrial pressure (RAP), left ventricular end-diastolic pressure (LVEDP), and total peripheral resistance (TPR) were increased. Renal blood flow was much reduced in the CHF as compared with the control group (5.1 +/- 0.8 vs. 9.1 +/- 0.6 ml/min.g, p less than 0.05). Similar falls in MAP were noted after fenoldopam in CHF (-13 +/- 2%) and control rabbits (-12 +/- 3%) due to falls in TPR. An increase in CO was observed in both groups, the rise being more pronounced in the CHF group (22 vs. 12%). Heart rate was unchanged by fenoldopam in CHF rabbits but increased in controls. After fenoldopam, CHF rabbits exhibited significantly greater increases in blood flow to each of the three vascular beds studied: renal (113 +/- 27% vs. 7 +/- 13%), mesenteric (249 +/- 60% vs. 15 +/- 19%) and cerebral (145 +/- 13% vs. 12 +/- 12%). Plasma renin and norepinephrine (NE) levels increased after fenoldopam in both control and CHF rabbits. These results show that acute administration of fenoldopam produces favourable systemic and regional hemodynamic responses in rabbits with low output heart failure. However, long-term benefit remains to be demonstrated, particularly considering the hormonal responses.

Animals↗

PubMed1988

The haemodynamic profile of cromakalim in the cat.

The haemodynamic profile of the novel antihypertensive agent, cromakalim (BRL 34915), has been studied in conscious and anaesthetised cats. Given orally (0.03 and 0.06 mg/kg) to conscious cats and by intravenous infusion (0.002 mg/kg/min for 7-10 min) to anaesthetised animals, cromakalim reduced arterial pressure (AP; systolic/diastolic) and total peripheral resistance (TPR) while increasing cardiac output (CO) via both its components [heart rate (HR) and stroke volume (SV)]. In both models, HR changes were minimal for reductions of AP approaching 20 mm Hg. In a second group of conscious cats, cromakalim increased mean renal blood flow (MRBF) at hypotensive doses (0.03 and 0.06 mg/kg orally); HR was only significantly raised following the higher dose of cromakalim. In anaesthetised animals, intravenously infused cromakalim had little effect on central venous pressure and increased cardiac contractility. The data indicate that cromakalim lowers AP by reducing TPR with minimal increase in HR. In addition, cromakalim has a potentially beneficial effect on MRBF.

Anesthesia↗

PubMed1989

Effects of the novel beta-adrenergic partial agonist alifedrine on cardiac performance in dogs with acute ischemic left ventricular failure.

Acute ischemic left ventricular failure was induced in dogs by coronary embolization with plastic microspheres, resulting in reduced cardiac output (CO), increased left ventricular end-diastolic pressure (LVEDP), pulmonary capillary pressure (PCP), and total peripheral resistance (TPR). Intravenous (i.v.) administration of alifedrine, a beta-adrenergic partial agonist (0.3 mg/kg as bolus and 0.3 mg/kg/h as infusion), significantly improved performance of the failing heart. Left ventricular contractility was increased up to 50%, heart rate (HR) up to 28%, and CO up to 30%. LVEDP, PCP, and TPR were markedly decreased. Myocardial oxygen consumption was increased only to a minor degree despite the positive inotropic effect; coronary flow was augmented up to 26%. Thus, alifedrine in this model markedly improved left ventricular function by balanced stimulation of the myocardium and reduction of pre- and afterload.

Acute Disease↗

PubMed1989

Hemodynamic, renal, and hormonal effects of 8-Br-cyclic GMP in conscious dogs with and without congestive heart failure.

In conscious dogs, we examined the hypothesis that the effects of atrial natriuretic peptide (ANP) are mediated by cyclic GMP and tested whether stimulation of the intracellular pathway beyond the ANP receptor level still exerts ANP-like effects during tolerance to ANP in heart failure. We studied the hemodynamic, renal, and hormonal effects of the cyclic GMP analogue 8-bromo-cyclic GMP (8-Br-cyclic GMP) in conscious dogs before and after induction of congestive heart failure by right ventricular pacing. In healthy dogs, 8-Br-cyclic GMP (1-100 micrograms/kg/min) dose-dependently decreased mean arterial pressure (MAP -19% by 100 micrograms/kg/min) and total peripheral resistance (TPR -22%) with no change in cardiac output (CO) and right atrial pressure, increased urine flow (UF 52%), and sodium excretion (UNaV 135%). Plasma renin (62%) and norepinephrine (NE 24%) were increased. In dogs with heart failure, 8-Br-cyclic GMP induced a similar arteriolar dilation (MAP -16%, TPR -23%) with no change in CO and preload. However, the effects on renal excretory function were abolished or markedly attenuated (UF -4%, UNaV 7%). Plasma renin (163%) and aldosterone (40%) were increased. Our findings support the hypothesis that the renal effects of ANP are mediated by cyclic GMP in vivo. The attenuation of renal effects of 8-Br-cyclic GMP in heart failure does not prove but is in agreement with the hypothesis that an intracellular defect beyond cyclic GMP production might be involved in the tolerance to ANP in heart failure.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1989

Hemodynamic effects of a poly(ethylene oxide) drag-reducing polymer, Polyox WSR N-60K, in the open-chest rat.

The acute hemodynamic effects of an intravenously (i.v.) injected poly(ethylene oxide), Polyox WSR N-60K (dose 50 mg/kg), were studied in the open-chest rat anesthetized with sodium pentobarbital. The injectate is one of four drag-reducing polymers known to augment in vitro blood flow under a constant pressure gradient; the others are an anionic polyacrylamide (Separan), a rhamnogalactogalacturonan (RGGu), and a deoxyribonucleic acid (calf thymus DNA). RGGu and Separan both augment cardiac output in the rat. Aortic blood flow, measured with an electromagnetic flow probe mounted on the ascending aorta, increased immediately after administration of the polymer and remained above control flow for at least 1 h. A small sustained decrease in heart rate (HR) was associated with a prolongation of systole. Ventricular and arterial blood pressures increased progressively over the 2-h postinjection period. Total peripheral resistance (TPR) initially decreased but then increased continuously throughout the experimental period, eventually surpassing the control value. Although the in vivo effects of Polyox differ from those of RGGu and Separan, the effects of the three macromolecules on aortic flow and TPR are similar at least in the first hour. Because the three substances are chemically dissimilar, these results further support the hypothesis that the primary mechanism responsible for the hemodynamic changes caused by some drag-reducing polymers--apparently limited to those with molecular lengths approaching 100 microns--is physical in nature.

Animals↗

PubMed1990

A novel orally active dopamine prodrug TA-870. III. Positive inotropic effect and cardiorenal selectivity in anesthetized dogs.

The effect of TA-870, a novel dopamine prodrug, on the cardiovascular system was studied in anesthetized open- and closed-chest dogs. Intraduodenal administration of less than or equal to 12 mg/kg TA-870 to anesthetized dogs increased left ventricular (LV) dP/dtmax and dP/dt/Pmax. Furthermore, at a lower dose of TA-870 (2 mg/kg), renal vascular resistance (RVR) decreased and renal blood flow (RBF) increased. Similarly, total peripheral resistance (TPR) decreased and cardiac output (CO) increased at less than 4 mg/kg. In an intravenous cumulative dose-response study of TA-870, the plasma-free-dopamine concentration was elevated depending on the dose of TA-870. Renal vasodilation occurred at a low plasma-free-dopamine concentration, whereas a positive inotropic action required higher plasma-free-dopamine. However, the dose-response curve for LVdP/dt/Pmax was steeper than that for RBF or CO. Heart rate was less affected than LVdP/dt/Pmax in open-chest dogs and decreased in closed-chest dogs. Propranolol strongly inhibited the effect of TA-870 on LVdP/dt/Pmax. It also inhibited the effects of TA-870 on TPR and CO to a lesser extent, and the remaining effects were almost completely inhibited by an additional treatment with the dopamine blocker, RS-sulpiride. In conclusion, TA-870 increased myocardial contractility and output by the enteral route, and the latter effect was produced at lower doses with the help of peripheral vasodilation due to the activation of dopamine receptors.

Anesthesia↗

PubMed1990

Hemodynamic, hormonal, and renal effects of the prostacyclin analogue iloprost in conscious dogs with and without heart failure.

To test the efficacy of exogenous prostaglandins for vasodilator therapy in heart failure, we studied the effects of the prostacyclin-derivative iloprost (1.5-150 ng/kg/min) in seven conscious dogs before and after induction of heart failure by right ventricular pacing (250/min. 10 days). In healthy dogs, iloprost (150 ng/kg/min) decreased mean arterial blood pressure (MAP) (-45%) by a decrease in total peripheral resistance (TPR) (-55%), and increased cardiac output (CO) (+24%) and heart rate (HR) (+20%) with no effect on right atrial and pulmonary arterial pressures (RAP, PAP). Plasma norepinephrine (NE) (+47%), renin (+351%), and aldosterone (+126%) were increased. Urine flow (-70%) and Na excretion (-53%) were decreased. Iloprost (15 ng/kg/min) increased renal blood flow (RBF) (+29%), but did not change glomerular filtration rate (GFR). In dogs with heart failure, iloprost decreased arterial BP (-31%), TPR (-42%) and pulmonary vascular resistance (-28%) and increased CO (+29%), with no change in RAP and PAP. Plasma NE (+34%), renin (+385%), and aldosterone (+146%) were increased. RBF was unchanged. GFR (-24%) and filtration fraction (FF) (-30%) were decreased, as was urine flow (-65%). In experimental heart failure, iloprost is a potent arteriolar dilator, increasing CO with no preload effect. These beneficial effects are limited, however, by further neurohumoral activation and deterioration of renal function.

Analysis of Variance↗

PubMed1990

Antiischemic and hemodynamic effects of intravenous isradipine, a new calcium antagonist, in coronary heart disease: a comparative double-blind cross-over study with nifedipine.

In a double-blind cross-over study, 10 patients with stable angina pectoris owing to coronary heart disease were investigated in supine position during rest and bicycle exercise for the effect of 0.4 mg of intravenous (i.v.) isradipine in comparison to 2 mg i.v. nifedipine on cardiac hemodynamics and myocardial ischemia. At rest, both drugs significantly decreased total peripheral resistance (TPR) and mean arterial blood pressure (MAP), whereas heart rate (HR) increased. The pressures and resistance of the pulmonary circulation remained uninfluenced at rest. During symptom limited-exercise, both medications reduced TPR despite an unchanged MAP. Mean pulmonary artery pressure decreased significantly after both medications, whereas right atrial pressure (RAP), pulmonary capillary wedge pressure (PCWP), and pulmonary vascular resistance (PVR) decreased significantly only after nifedipine. The improvement of mean ischemic ST-segment depression averaged 44 +/- 6% (mean +/- SEM, p less than or equal to 0.01) after nifedipine and 45 +/- 7% (p less than or equal to 0.01) after isradipine. The time until angina appeared increased after isradipine by 89 +/- 28% (p less than or equal to 0.05) and after nifedipine by 105 +/- 42% (p less than or equal to 0.01). Significant differences between the two medications appeared only for cardiac output (CO) at rest (p less than or equal to 0.05), during which state the increase after isradipine was higher than after nifedipine, and for exercise HR (p less than or equal to 0.01), during which state only nifedipine induced a significant increase in frequency. We conclude that at the chosen dosages the hemodynamic and antiischemic effects of isradipine are similar to the effects that occur after nifedipine.

Calcium Channel Blockers↗

PubMed1990

Atrial natriuretic factor blocks the pressor action of endothelin.

The present study was designed to determine the pharmacologic effects of rat atrial natriuretic factor (r-ANF; 250 ng/kg/min), endothelin-3 (ET-3; 340 ng/kg/min), and combined r-ANF and ET-3 infusion on cardiac hemodynamics and renal function in anesthetized rats. The change in mean arterial pressure (delta MAP) was 13 +/- 2 mm Hg during ET-3 infusion alone. Delta MAP was -9 +/- 2 mm Hg during r-ANF infusion alone. Combined infusion of ET-3 and r-ANF resulted in a change in MAP of -7 +/- 3 mm Hg. The decrease in MAP during combined infusion of ET-3 and r-ANF occurred due to a decrease in cardiac output. Infusion of r-ANF did not block the cardiac output. Infusion of r-ANF did not block the ET-3-induced increase in total peripheral resistance (TPR). Infusion of r-ANF alone resulted in an 11-fold increase in urinary sodium excretion. ET-3 infusion completely blocked the ANF-induced natriuresis in part by markedly decreasing the glomerular filtration rate (GFR). ET-3 or r-ANF infusion alone resulted in two- or eightfold increases, respectively, in circulating r-ANF levels compared to vehicle alone. However, combined infusion of r-ANF and ET-3 resulted in a dramatic 27-fold increase in circulating r-ANF when compared to levels obtained during vehicle infusion alone. The present study demonstrates that at pharmacologic levels, r-ANF blocks the pressor action of ET-3 by decreasing cardiac output rather than TPR. Furthermore, ET-3 blocks the natriuretic action of r-ANF, partly by decreasing GFR.

Anesthesia↗

PubMed1992

Hemodynamic and renal effects of the protein kinase inhibitor staurosporine in conscious rats.

To evaluate the pattern of hemodynamic responses produced by an inhibitor of protein kinase C (PKC), staurosporine 0.03-0.55 mg/kg was administered intravenously (i.v.) to conscious, normotensive rats chronically instrumented with vascular catheters for direct measurement of blood pressure (BP) and i.v. administration of drugs and either an aortic flow probe for measurement of cardiac output (CO) or miniaturized pulsed Doppler flow probes for measurement of hindquarter, renal, and mesenteric vascular resistances. Staurosporine decreased mean arterial pressure (MAP) and total peripheral resistance (TPR) and increased heart rate (HR) in a dose-dependent manner. Because staurosporine decreased resistance in all three vascular beds monitored (hindquarter, renal, and mesenteric), staurosporine is probably a nonselective vasodilator that decreases MAP by decreasing resistance in a number of peripheral vascular beds. Staurosporine produced biphasic effects on CO, dF/dtmax and peak aortic blood flow; these parameters were significantly increased at doses less than 0.3 mg/kg and decreased to levels equal to or significantly less than control values at doses greater than 0.3 mg/kg. In comparison, the calcium channel blocker nitrendipine decreased MAP and TPR and increased HR, CO, dF/dtmax, and peak aortic flow in a dose-dependent manner over the entire dose range (0.01-1 mg/kg i.v.). Staurosporine (0.3 mg/kg) and nitrendipine (1 mg/kg) produced similar changes in MAP (-44 +/- 3 and -33 +/- 2 mm Hg, respectively), yet staurosporine affected dF/dtmax to a lesser extent than nitrendipine (-5 +/- 36 and 390 +/- 46 ml/s/s, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaloids↗

PubMed1992

Prostaglandin E2 in dogs with heart failure: hemodynamic, hormonal, and renal effects.

To test the efficacy of exogenous prostaglandins for vasodilator therapy in heart failure, we studied the hemodynamic, hormonal, and renal effects of prostaglandin E2 (1.5-150 ng/kg/min) in six conscious dogs before and after induction of heart failure by right ventricular pacing (250 beats/min, 10 days). In healthy dogs, PGE2 decreased the mean arterial pressure (MAP) by a reduction in total peripheral resistance (TPR), increased cardiac output (CO), stroke volume (SV), and heart rate with no effect on right atrial pressure (RAP). Plasma levels of renin (PRC) and norepinephrine (NE) were increased at the highest dosage. Renal plasma flow (RPF) and sodium excretion (UNaV) were augmented without a change in the glomerular filtration rate (GFR) and urine flow (UF). In dogs with heart failure, PGE2 lowered the MAP and TPR and elevated the CO and SV without an effect on the RAP, PRC, and NE. The RPF and GFR were not changed, but the increase in UNaV was preserved and UF significantly augmented. In experimental heart failure, PGE2 increases the CO due to arteriolar dilation and afterload reduction without inducing further neurohumoral activation and exerts potent natriuretic and diuretic action. Therefore, PGE2 may have beneficial effects in heart failure therapy.

Animals↗