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M Pfaffendorf

Publications and source records attributed to M Pfaffendorf.

At least 73 records · Page 4Linked to original sources
PubMed1996

The influence of hyperthyroidism on beta-adrenoceptor-mediated relaxation of isolated small mesenteric arteries.

We investigated the influence of hyperthyroidism on relaxant responses of small mesenteric resistance arteries to beta-adrenoceptor agonists and to compounds stimulating the corresponding second-messenger system. Hyperthyroidism was induced by feeding rats for 28 days with 5 mg/kg L-thyroxine (T4)-containing rat chow. This treatment produced a stable hyperthyroid state, as indicated by several biochemical/metabolic and haemodynamic parameters. Preparations of small mesenteric arteries were mounted in an isometric wire myograph. Subsequently, concentration-effect curves were determined for isoproterenol, noradrenaline and salbutamol as well as for forskolin, dibutyryl-cAMP and theophylline. We also determined concentration-effect curves to the beta-adrenoceptor agonists in the presence of ICI 118,551 and CGP 20712A (i.e., in the presence of a selective beta 2- and beta 1-adrenoceptor antagonist, respectively). Apparent pA2-values were calculated to determine which beta-adrenoceptor subtype causes vasodilation. These experiments indicate that beta-adrenoceptor-mediated vasodilation involves both beta 1- and beta 2-adrenoceptors in mesenteric resistance vessels of both hyperthyroid and control rats. In our experiments hyperthyroidism has a sensitizing influence on vascular responses induced by the beta-adrenoceptor agonist isoproterenol and the selective beta 2-adrenoceptor agonist salbutamol. Sensitization to isoproterenol was abolished in the presence of ICI 118,551, whereas it was emphasized in the presence of CGP 20712A. Although this was not fully supported by the results obtained with noradrenaline, these results indicate that the sensitization to beta-adrenoceptor agonists is probably limited to the beta 2-adrenoceptor/G-protein complex and not associated with alterations of the corresponding second messenger system.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1996

Cardiac iodine-123 metaiodobenzylguanidine uptake in animals with diabetes mellitus and/or hypertension.

The aim of the present study was to evaluate the use of the noradrenaline analogue iodine-123 metaiodobenzylguanidine ([123I]MIBG) for the assessment of cardiac sympathetic activity in the presence of diabetes mellitus and/or hypertension in animal models. One model used Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) rendered diabetic at 12 weeks of age by an intravenous injection of streptozotocin (STZ). The other model used lean and obese Zucker rats. In all groups basic haemodynamic values were established and animals received an intravenous injection of 50 microCi [123I]MIBG. Initial myocardial uptake and wash-out rates of [123I]MIBG were measured scintigraphically during 4 h. After sacrifice, plasma noradrenaline and left cardiac ventricular beta-adrenoceptor density was determined. The diabetic state, both in STZ-treated rats (direct induction) and in obese Zucker rats (genetic induction), appeared to induce a lower cardiac density of beta-adrenoceptors, indicative of increased sympathetic activity. Cardiac [123I]MIBG then showed increased wash-outs, thereby confirming enhanced noradrenergic activity. This parallism of results led to the conclusion that [123I]MIBG wash-out measurements could provide an excellent tool to assess cardiac sympathetic activity non-invasively. However, in hypertension (WKY vs SHR), both parameters failed to show parallelism: no changes in beta-adrenoceptor density were found, whereas [123I]MIBG wash-out rate was increased. Thus, either [123I]MIBG washout or beta-adrenoceptor density may not be a reliable parameter under all circumstances to detect changes in the release of noradrenaline. Changes in the initial uptake of [123I]MIBG were observed as well. This may be a good marker for the disappearance of cardiac innervation, but it seems not to be a good parameter for distinguishing between loss of sympathetic innervation and enhanced uptake of noradrenaline in pathological conditions.

3-Iodobenzylguanidine↗
PubMed1996

Function of cryopreserved arterial allografts under immunosuppressive protection with cyclosporine A.

PURPOSE: Cryopreserved arterial allografts may be used for arterial reconstructive procedures. In this experimental study cryopreserved arteries were used as autografts and as allografts with or without immunosuppression with cyclosporine A. METHODS: In group A (three dogs, six bilateral grafts) cryopreserved carotid artery autografts were implanted. In groups B and C female mongrel dogs (three dogs and six bilateral grafts in each group) received cryopreserved male carotid artery allografts. Dogs in group C were treated with cyclosporine A (25 mg/kg/day). After 3 months of implantation patency was assessed by angiography. Contractile responses to KCl and phenylephrine (Phe) and the endothelium-dependent relaxation response to methacholine (Met) were examined in segments of the grafts after excision. Medial thickness was assessed semiquantitatively. The grafts were stained for sex chromatin analysis to determine the origin of cells in allografts. RESULTS: Patency: group A, 100% (6 of 6), group B, 66.6% (4 of 6), and group C, 100% (6 of 6). Functional responses: before implantation, after thawing, 2.7 +/- 0.5 mN (KCl), 4.8 +/- 1.0 mN (Phe), and 0.0% +/- 0.0% (Met), group A, 36.9 +/- 10.6 mN (KCl), 31.5 +/- 14.4 mN (Phe), and 59.3% +/- 20.4% (Met), group B, 0 for all agents used, group C, 34.0 +/- 7.5 mN (KCl), 28.8 +/- 7.0 mN (Phe), and 46.2% +/- 3.2% (Met). Morphologic characteristics: the media of grafts in group B showed significant thinning (p < 0.05). Smooth-muscle cells in vessel walls of grafts in group C were of female origin. CONCLUSION: Arteries showed no function and loss of endothelial integrity after cryopreservation and thawing. After 3 months of implantation cryopreserved arterial autografts and allografts under immunosuppressive treatment with cyclosporine A showed 100% patency and return of functional responses resulting from repopulation of grafts by host cells.

Animals↗
PubMed1996

Effect of phosphodiesterase inhibitors on human arteries in vitro.

In the present study, we investigated if the relaxant effects of phosphodiesterase (PDE) III inhibitors on human vessels could be inhibited by a nitric oxide synthase blocker, L-NAME, or by a blocker of ATP-sensitive potassium channels (KATP), glibenclamide. The experiments were performed using an isometric myograph in isolated human s.c. small arteries obtained from healthy donors. After a priming procedure consisting of exposure to high potassium (120 mmol litre-1) solutions, phenylephrine 10 mumol litre-1 and an equilibrium period of 30 min, the preparations were contracted with a thromboxane A2 mimetic agent, U46619 1 mumol litre-1. Subsequently, cumulative concentration-response curves were constructed for the selective PDE III inhibitors amrinone, milrinone and enoximone, and for theophylline and dipyridamole, with and without the addition of L-NAME 100 mumol litre-1 or glibenclamide 1 mumol litre-1. Addition of L-NAME to the organ bath resulted in significantly higher pEC50 values (-log of the concentration required for 50% relaxation) for milrinone compared with the control: 2.77 (SEM 0.24) mol litre-1 (n = 5) vs 3.49 (0.17) mol litre-1 (n = 7) (P < 0.05). There was no significant difference between any other group. From our data we conclude that the relaxant properties of amrinone, enoximone, theophylline and dipyridamole are not dependent on nitric oxide release or on interaction with KATP channels. However, the effect of milrinone may be partly endothelium-dependent in human vessels in vitro.

Adolescent↗
PubMed1996

Influence of nifedipine on pressor responses induced by different alpha-adrenoceptor agonists and angiotensin II in pithed diabetic hypertensive rats.

OBJECTIVE: Both intracellular and extracellular sources of calcium are involved in the activation of contraction in vascular smooth muscle. In the diabetic or hypertensive state, or both, changes induced in calcium handling by various types of agonists may vary considerably. METHODS: We investigated in which manner L-type calcium-channel blockade with nifedipine influences the pressor effects of the alpha 1-adrenoceptor agonists cirazoline and ST 587, the alpha 2-adrenoceptor agonist UK 14.304 and angiotensin II, all exerting a differential influence on calcium homeostasis, in pithed spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats rendered diabetic by an injection of 55 mg/kg streptozotocin. RESULTS: In diabetic WKY rats and SHR, the maximal pressor response was impaired for all agonists. The hypertensive state enhanced the maximal pressor response to all agonists. No difference was found in the nifedipine-induced depression of the pressor response to cirazoline and angiotensin II in the four groups of rats. The maximal pressor responses to ST 587 and UK 14.304 were more effectively depressed by administration of 0.3 mg/kg nifedipine both in diabetic WKY rats and in diabetic SHR than they were in their non-diabetic controls. CONCLUSIONS: Hypertension was associated with enhanced pressor response, whereas the diabetic state counteracted this effect. The pressor responses in pithed diabetic and diabetic hypertensive rats were clearly more dependent on the nifedipine-sensitive calcium influx than were those in their non-diabetic controls.

Adrenergic alpha-Antagonists↗
PubMed1996

Vascular responsiveness in isolated perfused kidneys of diabetic hypertensive rats.

OBJECTIVE: The aim of this study was to investigate whether diabetes and hypertension cause additive effects in the responses to various vasoconstrictor and vasodilator agents, in isolated perfused kidneys obtained from streptozotocin (STZ)-diabetic Wistar-Kyoto (WKY) rats and from diabetic spontaneously hypertensive rats (SHR). METHODS: SHR and WKY rats were administered STZ 55 mg/kg by intravenous injection into a lateral tail vein at age 12 weeks. Eight weeks later the kidneys were isolated and perfused via the left renal artery with a physiological salt solution. Renal perfusion pressure was measured continuously. Concentration response curves were plotted for various vasoconstrictor and vasodilator agents. RESULTS: Both the diabetic and the hypertensive state were associated with an increased wet kidney weight. The contractile responses of the renal arterial system to phenylephrine (PhE), serotonin (5-HT) and angiotensin II (Ang II) in terms both of the maximal rise in perfusion pressure (mmHg) and of the sensitivity (log EC50) were the same in preparations from diabetic WKY rats and in those from normoglycaemic WKY rats. The maximal contractile responses both to PhE and to Ang II were enhanced in kidneys from SHR compared with those in kidneys from their normotensive controls, whereas simultaneously occurring diabetes impaired this sensitization. After precontraction with 3 x 10(-6) mol/l PhE both endothelium-dependent (methacholine) and endothelium-independent (sodium nitroprusside) vasodilator drugs caused the same vasodilator response in the preparations taken from the four groups of animals. CONCLUSION: In isolated perfused kidneys obtained from STZ-diabetic WKY rats and SHR, the isolated diabetic state did not influence the vasoconstriction caused by various agonists. However, the enhanced vascular reactivity in the hypertensive state was blunted by simultaneously occurring diabetes mellitus. Endothelium-dependent and -independent vasorelaxation in this model was not affected neither by the hypertensive nor by the diabetic state.

Animals↗
PubMed1996

Contractile responses to various stimuli in isolated resistance vessels from simultaneously hypertensive and streptozotocin-diabetic rats.

Diabetes mellitus and hypertension are common chronic diseases that frequently occur simultaneously. The induction of streptozotocin (STZ) diabetes mellitus in spontaneously hypertensive rats (SHR) offers the opportunity to investigate the influence of both entities in a reproducible manner. We investigated the effects of various vasoconstrictors on isolated small arteries from the mesenteric vascular bed of normotensive rats (Wistar-Kyoto rats, WKY) and SHR with chronic (8 weeks), STZ-induced diabetes mellitus. No consistent changes in hemodynamic parameters of the (STZ-) normotensive and (STZ-) hypertensive rats were noted. The K(+)-normalization procedure yields the individual optimal lumen diameter, which was the same for the arteries of the four groups of rats. The passive wall tension resulting from this normalization procedure was higher only in preparations from the control hypertensive group as compared with those from the control normotensive rats. Morphological investigations showed that small arteries from control SHR had an increased tunica media thickness as compared with those of control WKY; the STZ-WKY had an increased tunica media thickness as compared with preparations from control WKY. The vasoconstriction caused by alpha 1-adrenoceptor stimulation [norepinephrine (NE), methoxamine] and serotonin is unchanged in chronic experimental diabetes. The diabetic state reduced the sensitivity [-log EC50(M)] for the concentration-response curves (CRC) of calcium chloride. The CRC of potassium chloride indicated the same sensitivities, but maximal active wall tensions of vessels from STZ-SHR were reduced as compared with those from STZ-WKY. The well-known enhancement of the effects of various contractile stimuli caused by hypertension could not be demonstrated for the isolated small arteries used in the present study, although a nonsignificant tendency was observed. However, the STZ-diabetic state did not cause important additional pharmacodynamic changes, despite the morphological alterations in those vessels.

Adrenergic alpha-Agonists↗
PubMed1996

Influence of the low thyroid state in diabetes mellitus on cardiac function and inotropic responsiveness to alpha 1-adrenoceptor stimulation: comparison with the role of hypothyroidism alone.

The hypothyroid state accompanying diabetes mellitus has been suggested to be partly responsible for the diabetes-induced metabolic, hemodynamic, and pharmacological cardiovascular changes. We assessed the effectivity of streptozotocin (STZ) to induce diabetes mellitus and a hypothyroid state. Furthermore, we investigated the influence of diabetes and hypothyrodism on cardiac function and the inotropic responsiveness to the alpha 1-adrenoceptor agonist cirazoline in isolated perfused hearts. Fasted or nonfasted Wistar rats were made diabetic with STZ 20, 40 or 60 mg/kg intravenously (i.v.). Another group was made hypothyroid by addition of 6-n-propyl-2-thiouracil (PTU) to their drinking water. Rats receiving PTU became hypothyroid, whereas rats receiving STZ became simultaneously diabetic and hypothyroid. Basal functional parameters obtained in isolated perfused hearts were not influenced by diabetes, whereas maximal contractility was reduced in hearts obtained from hypothyroid animals. Cardiac inotropic responses to cirazoline were increased in diabetic rats, whereas responses in hypothyroid rats were not different from those in hearts obtained from control animals. Although diabetes mellitus and hypothyroidism are associated with various similar metabolic and haemodynamic parameters, the increased inotropic response to alpha 1-adrenoceptor stimulation as observed in isolated perfused hearts of diabetic rats cannot be explained by the decrease in serum thyroxine levels.

Adrenergic alpha-Agonists↗
PubMed1996

Pharmacodynamic behaviour of isolated resistance vessels obtained from hypertensive-diabetic rats.

The influence of various vasodilator and constrictor drugs was studied in isolated mesenteric arteries obtained from obese and lean Zucker rats. The obese Zucker rats were moderately hypertensive and their isolated small arteries were not hypertrophied. All vasoconstrictor agents studied (noradrenaline, methoxamine, serotonin, calcium chloride, potassium chloride) caused the same effects in isolated arteries taken from obese and lean (control) Zucker rats; respectively. In vessels from obese Zucker rats, the vasodilator responses to sodium nitroprusside, methacholine, the K(+)-channel opener cromakalim and nifedipine were the same as in control preparations. In conclusion, isolated mesenteric arteries from obese Zucker rats do not show relevant structural changes, and the pharmacodynamic behaviour of such vessels appears to be the same as that of control preparations. Neither the diabetic hyperinsulinaemic state not the hyperlipoproteinaemia in the obese Zucker rats appear to cause serious vascular damage.

Animals↗
PubMed1996

Direct positive chronotropic effects of angiotensin II and angiotensin III in pithed rats and in rat isolated atria.

1. The direct positive chronotropic effects of angiotensin II (AII) and its degradation products angiotensin III (AIII) and angiotensin IV (AIV) were established in pithed rats and in rat spontaneously beating right atria. 2. In pithed rats, AII, AIII and AIV caused dose-dependent tachycardia with similar maximal responses (110 beats min-1). The beta-adrenoceptor antagonist propranolol (3.37 x 10(-6) mol kg-1) but not the alpha 1-adrenoceptor antagonist prazosin (2.38 x 10(-7) mol kg-1) significantly reduced these effects (P < 0.05; n = 7-8), but 20-25% of the responses could not be blocked by propranolol. 3. In isolated atria, AII, AIII and AIV caused concentration-dependent increases in beating rate with similar maximal responses to AII and AIII (34.3 +/- 0.4 and 34.7 +/- 0.4 beats min-1; n = 9-10), and a lower maximal response to AIV (26.8 +/- 0.6 beats min-1; P < 0.05; n = 8). AIII was about 9 times less potent than AII, whereas AIV proved approximately 3800 times less potent than AII. Neither propranolol (1 microM) nor prazosin (1 microM) could influence the effects of the angiotensin peptides. 4. In isolated atria, the selective AT1-receptor antagonist, losartan (10, 100 and 300 nM) caused parallel rightward shifts of the concentration-response curves for AII and AIII, whereas the selective AT2- receptor antagonist PD123177 (1 microM) did not influence the effects of AII and AIII. The aminopeptidase-A and -M inhibitor amastatin (10 microM), significantly steepened the slope of the AIII curves and increased the potency of AIII about 6 fold. Amastatin did not influence the responses to AII. 5. Our results indicate that both in vivo and in vitro, exogenous AII and AIII induced a direct dose-dependent chronotropic effect, which is independent of the adrenergic system. This chronotropic effect is mediated by AT1-subtype receptors.

Adrenergic alpha-Antagonists↗
PubMed1996

Opposite influences of hypertension and diabetes mellitus on pressor responses induced by different alpha-adrenoceptor agonists and angiotensin II in pithed rats.

Hypertension is often present in the diabetic individual and it is known to aggravate the vascular complications associated with diabetes. The pressor responses to two alpha 1-adrenoceptor agonists (ST587 and cirazoline), two alpha 2-adrenoceptor agonists (azepexole dihydrochloride (B-HT933) and UK14.304) and angiotensin II were investigated in pithed spontaneously hypertensive rats (SHR) and in pithed normotensive Wistar Kyoto rats (WKY) made diabetic by a single i.v. injection (55 mg/kg) of streptozotocin (STZ). Two months after diabetes was induced, the effect of the agonists on basal diastolic blood pressure (DBP) was determined. In pithed diabetic WKY and SHR, the maximal pressor response was impaired for all agonists. The dose response curves were shifted to the right when compared with their non-diabetic controls. The hypertensive state enhanced the maximal pressor response to all agonists compared with non-hypertensive animals. Additional diabetes blunted this increase in the effects of ST587, B-HT933 and angiotensin II, but not in those of cirazoline and UK14.304. Hypertension caused a leftward shift of the dose response curve for ST587 when compared with the non-hypertensive state. However, this effect was not observed when diabetes was present as well. In conclusion, hypertension resulted in an enhanced pressor effect, possibly caused by vascular hypertrophy, whereas the diabetic state counteracted this effect.

Adrenergic alpha-Agonists↗
PubMed1996

Comparison of cholinergic vasodilator responses to acetylcholine and methacholine in the human forearm.

In order to study the contribution of the nitric oxide (NO)-pathway to cholinergic vasodilatation in the resistance vessels of the human forearm, we infused acetylcholine (ACh; 0.1 1000 ng/kg/min) or methacholine (MCh; 0.1 A 100 ng/kg/min) in the presence of saline, the NO-scavenger and guanylate cyclase inhibitor methylene blue (MB; 1000 ng/kg/min), or the NO-synthase inhibitor NG-monomethyl-L-arginine (L-NMMA; 30 micrograms/kg/min) into the brachial artery of normotensive volunteers (n = 32), using venous occlusion plethysmography. We calculated the plasma concentrations of the infused compounds to obtain EC50-values (-log mol/l). ACh and MCh both caused concentration-dependent vasodilatation (EC50-values of 6.43 +/- 0.05 and 7.24 +/- 0.08, respectively). MB (13 mumol/l) did not change basal forearm blood flow (FBF) when administered alone, but it markedly potentiated the vasodilator response to ACh, shifting the concentration-response curve (CRC) leftwards by 1.5 log-step (p < 0.001). MB did not affect MCh-induced vasodilatation. L-NMMA (1 mmol/l) alone caused dose-dependent vasoconstriction that was subject to tachyphylaxis. In addition, L-NMMA caused a steepening of the slopes of the CRCs of ACh, and MCh L-NMMA attenuated the ACh-/MCh-induced vasodilator responses in the lowest concentration ranges (p < 0.05) only, but did not alter the response at higher concentrations. The 10-fold higher potency of MCh compared to ACh can be explained by the more rapid degradation of ACh by cholinesterases. The observation that high concentrations of L-NMMA only affect vasodilation mediated by low concentrations of ACh or MCh, suggests a second mechanism in cholinergic vasodilatation, such as a direct effect on smooth muscle cells or the release of a relaxing factor other than NO.

Acetylcholine↗
PubMed1996

Effects of losartan on vasoconstrictor responses to angiotensin II in the forearm vascular bed of healthy volunteers.

OBJECTIVES: The angiotensin type 1 (AT1) receptor antagonist, losartan (orally administered), decreases vasoconstrictor effects of angiotensin II (Ang II). Oral losartan is converted into the active metabolite, Exp3174, which causes most of the antagonistic effects. Effects of losartan as such have not been studied after its intra-arterial administration in humans. Therefore, we investigated the effects of both intra-arterially and orally administered losartan on AT1-receptor-mediated vasoconstriction. METHODS: Forearm vascular resistance (FVR) was determined by venous occlusion plethysmography in 24 healthy subjects. Ang II (0.01, 0.1, 1.0, and 10.0 ng/kg/min) was infused into the brachial artery, before and after losartan, administered intra-arterially (dose range 100-3000 ng/kg/min) or orally (50 mg once daily for 5 days). RESULTS: Ang II concentration-dependently increased FVR (P < 0.05); tachyphylaxis did not occur. Losartan alone did not change FVR. Intra-arterially infused losartan dose-dependently inhibited Ang-II-induced vasoconstriction. At a concentration of 10(-8) M Ang II, losartan reduced FVR, as a percentage of baseline values, from 287 +/- 30 to 33 +/- 8% (mean +/- s.e.m.; P < 0.05). Orally given losartan reduced FVR from 297 +/- 40 to 73 +/- 19% (P < 0.05). CONCLUSIONS: Losartan, intra-arterially administered, causes no effect on baseline vascular resistance, but markedly inhibits Ang-II-induced vasoconstriction in the human forearm vascular bed. Relatively high doses of intra-arterial losartan were required when compared to the antagonism by the orally administered drug. These data indicate that Ang-II-induced vasoconstriction is mediated by AT1-receptors, which are blocked by losartan. The more effective antagonism exerted by oral losartan is presumably explained by the formation of Exp3174. Endogenous Ang II does not contribute to baseline vascular tone in healthy, sodium-replete, subjects.

Administration, Oral↗
PubMed1996

Attempts to improve the selectivity of calcium antagonistic drugs.

The dihydropyridine calcium antagonists differ in respect to their structures as well as their pharmacological profiles. An improved vascular selectivity has been claimed for some of the newer agents (amlodipine, felodipine, isradipine, lacidipine, lercanidipine, manidipine and nicardipine), implying that these agents exert a stronger action on the resistance and coronary arteries than on myocardial and nodal structures. By virtue of their antihypertensive effects, calcium antagonists should be considered as renal protective. Such a renal protective potential has been demonstrated in renal insufficiency and toxicity caused by cancer chemotherapy, radiocontrast agents, cyclosporine or aminoglycoside antibiotics. Furthermore, calcium antagonists may also have a protective effect on donor kidneys in kidney transplantation. Among the newer dihydropyridines, manidipine has been suggested as possessing a certain degree of renal selectivity. This claim is based mainly on animal experimental studies and has to be substantiated in the clinic. From the therapeutic point of view, the concept of renal selectivity for calcium antagonists may be of considerable interest.

Calcium Channel Blockers↗
PubMed1995

Relaxant effect of levcromakalim in isolated human small subcutaneous arteries.

The effect of levcromakalim, an ATP-sensitive K+ channel opener, on isolated subcutaneous arteries from mammary tissues obtained from female patients undergoing reconstructive breast surgery was investigated. The small arteries were preserved in the University of Wisconsin (UW) solution. The contractile responses to K+ and 9,11-dideoxy-11a,9a-epoxy-methano-prostaglandin F2 alpha (U46619) and the relexant responses to levcromakalim and to the endothelium-dependent vasodilator, methacholine, in these arteries remained fully intact after preservation in UW solution for at least 5 days. The pD2 value and maximal relaxation obtained from the concentration-response curve of levcromakalim (n = 7) were 5.78 +/- 0.23 and 81 +/- 6%, respectively. The vasodilator effect of levcromakalim was significantly antagonised by the ATP-sensitive K+ channel blocker, glibenclamide (1 and 3 microM). In conclusion, isolated human arteries contain ATP-sensitive K+ channels, which can be modulated by K+ channel openers and blockers. Subcutaneous small arteries, as used in our experiments, appear to be very suitable for pharmacological experiments.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1995

Sensitivity of cardiac tissues with moderate and advanced hypertrophy to calcium ions.

1. Prolonged existence of hypertension is known to induce a compensatory increase in cardiac weight, later followed by a loss of functional responsiveness to biological stimuli. 2. It was the aim of the present study to investigate the functional responses of hypertrophied hearts to rising levels of intracellular calcium. The experiments were performed using two different degrees of cardiac hypertrophy, the first as obtained in spontaneously hypertensive rats (SHR) of 18-20 weeks old, the second by using rats, 32-34 weeks old, with a surgically induced stenosis of the thoracic aorta (ASR). The ASR, which showed signs of overt heart failure, may be presented as a model for hypertension-induced end-stage cardiac hypertrophy. Age-matched normotensive Wistar-Kyoto rats (WKY) and sham-operated Wistar rats served as respective controls. 3. Different methods were employed such as increasing the extracellular Ca2+ concentration, stimulation of calcium influx by means of the calcium entry promoter Bay K 8644, or altering the sodium-calcium exchange by means of the sodium ionophore monensin. 4. The inotropic responses induced by increasing the extracellular Ca2+ concentration or provoked by the calcium entry promoter Bay K 8644 proved more pronounced in hearts taken from SHR of 18 weeks old than in those from normotensive control rats, whereas the response to monensin was found to be the same in both types of hearts. In the hearts of ASR, however, the inotropic responses to Ca2+, Bay K 8644 and monensin were strongly impaired. 5. These data demonstrate that in functional experiments the sensitivity to Ca2+, which represents the main pathway in establishing a contraction, is strongly reduced in advanced cardiac hypertrophy.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1995

Morphology and function of dog arterial grafts preserved in UW-solution.

OBJECTIVES: To assess the function of arterial grafts after prolonged preservation in the University of Wisconsin solution (UW), in vitro and in vivo. METHODS: Carotid arteries were harvested from dogs and stored for 1-21 days at 4 degrees C in UW (n = 10) or in PBS (0.9% NaCl, pH 7.4), (PBS) (n = 10). Slices were examined by lightmicroscopy (LM) and scanning electron microscopy (SEM). For viability testing, specimens were connected to an isometric force transducer (2 x n = 9). Contractile and relaxation responses were examined by adding phenylephrine (200 microM) and metacholine (200 microM), respectively. For in vivo studies (n = 41), 2.5cm carotid artery segments were implanted or orthotopically, as autografts and allografts, after 14 days of storage in UW or in PBS. Autologous veins were used as controls. After 28 days or 56 days, arteriography was performed and the grafts were excised for LM and SEM. RESULTS: The arterial endothelial layer remained intact after up to 14 days of storage in UW. In PBS, the endothelium was lost after 3 days. The functional response after 14 days storage in UW was approximately 50% vs. 0% after 14 days in PBS. In the autografts, total patencies (28 days + 56 days) were 100% (8/8) and 63% (5/8) for UW and PBS stored grafts, respectively. In the allografts, the UW and PBS preserved grafts showed total patencies of 86% (12/14) and 83% (5/6), respectively. Microscopically, the allografts showed fibrotic degeneration. CONCLUSIONS: Arteries are well preserved in UW up to 14 days of storage. Arterial autografts preserved in UW showed good patency and better integrity of the vessel wall after implantation, than grafts stored in PBS or allografts (without immunosuppressive therapy).

Adenosine↗