Biomedical subjects

W Durante

Publications and source records attributed to W Durante.

At least 37 records · Page 2Linked to original sources

PubMed1996

Platelet-derived growth factor regulates vascular smooth muscle cell proliferation by inducing cationic amino acid transporter gene expression.

Since recent studies demonstrated that platelet-derived growth factor (PDGF) induces vascular smooth muscle cell (SMC) proliferation by stimulating polyamine synthesis, we examined whether the transcellular transport of L-ornithine, the cationic amino acid precursor of polyamines, could regulate the mitogenic response of PDGF. Treatment of SMC with PDGF stimulated DNA and putrescine synthesis, and this was enhanced further by increasing the extracellular concentration of L-ornithine. The potentiating effect of L-ornithine was reversed by the competitive inhibitor of cationic amino acid transport, methyl-L-arginine, or by preventing putrescine formation with alpha-difluoromethylornithine. Cationic amino acid uptake by SMC was Na+-independent and was mediated by both a high and low affinity carrier system. Treatment of SMC with PDGF initially (0-2 h) decreased basic amino acid transport, while longer exposures (6-24 h) progressively increased uptake. Kinetic studies indicated that PDGF-induced inhibition was associated with a decrease in affinity for cationic amino acids, while the stimulation was mediated by an increase in transport capacity. Endogenous PDGF released by collagen-activated platelets likewise up-regulated cationic amino acid transport in SMC. Reverse transcriptase-polymerase chain reaction detected the presence of mRNA encoding two distinct cationic amino acid transporter (CAT) proteins, CAT-1 and CAT-2B. Treatment of SMC with PDGF strongly induced the expression CAT-2B mRNA and modestly elevated the level of CAT-1 mRNA. These results demonstrate that PDGF-induced polyamine synthesis and SMC mitogenesis are dependent on the transcellular transport of L-ornithine. The capacity of PDGF to up-regulate the transport of L-ornithine by inducing the expression of the genes for CAT-1 and CAT-2B may modulate its mitogenic effect by providing SMC with the necessary intracellular precursor for polyamine biosynthesis.

Amino Acid Sequence↗

PubMed1996

Regulation of interleukin-1-beta-stimulated inducible nitric oxide synthase expression in cultured vascular smooth muscle cells by hemostatic proteins.

Experiments were performed to examine the mechanism by which specific hemostatic proteins regulate the release of nitric oxide (NO) from interleukin-1 beta (IL-1beta) stimulated cultured rate aortic smooth muscle cells. Treatment of smooth muscle cells with IL-Beta stimulated inducible nitric oxide synthase (iNOS) mRNA expression, which preceded the release of NO (as measured by the accumulation of nitrite in the culture media). The cytokine-stimulated production of nitrite was blocked by the protein synthesis inhibitor cycloheximide, the transcriptional inhibitor actinomycin D, and the competitive inhibitor of NOS nitro-L-arginine. However, only actinomycin D inhibited IL-1beta-stimulated iNOS mRNA expression, Treatment of smooth muscle cells with IL-1beta in the presence of platelet derived growth factor or thrombin resulted in the inhibition of cytokine-stimulated expression of iNOS mRNA and NO release. The inhibitory effect of thrombin was reversed by hirudin and was mimicked by a 14 amino acid thrombin receptor activating peptide. In contract, the concomitant exposure of smooth muscle cells to IL-1beta-and plasmin resulted resulted in the potentiation of both IL-1beta-stimulated iNOS expression and NO generation. Finally, treatment of smooth muscle cells with IL-1beta in the presence of the hemostatic proteins did not affect the half-life of iNOS mRNA. These results demonstrate that specific protein components of the hemostatic system regulate IL- 1beta-stimulated iNOS mRNA expression in vascular smooth muscle cells. The capacity of hemostatic proteins to modulate the induction of vascular iNOS activity may play an important role in governing the release of NO and regulating thrombogenesis in vivo.

Amino Acid Sequence↗

PubMed1996

Differential regulation of L-arginine transport and nitric oxide production by vascular smooth muscle and endothelium.

Since NO production is dependent on the availability of L-arginie, we examined whether L-arginine transport and NO synthesis are coregulated by vascular smooth muscle cells and endothelial cells cultured from the same vessel wall source. L-Arginine transport by both bovine aortic smooth muscle cells (BASMCs) and endothelial cells (BAECs) was primarily Na+ independent (approximately 70%) and was mediated by both a high- and low-affinity transport system. Treatment of BASMCs with tumor necrosis factor-alpha (TNF-alpha) or interleukin-1 beta (IL-1 beta) resulted in a significant increase in L-arginine transport (approximately 20%) and in the induction of NO release. Exposure of BASMCs to interferon gamma (IFN-gamma) or lipopolysaccharide (LPS) also stimulated NO release but did not affect L-arginine transport. In contrast, incubation of BAECs with TNF-alpha or LPS strikingly enhanced L-arginine uptake (2.5-fold), whereas IL-1 beta and IFN-gamma had no effect. Treatment of BAECs with any of the inflammatory mediators did not stimulate NO production. These results demonstrate that L-arginine uptake and NO synthesis by these cells are differentially regulated. In BASMCs, the coinduction of L-arginine transport and NO formation may function to provide increased levels of substrate to the cell during activation of the NO synthase enzyme. In contrast, the selective stimulation of L-arginine uptake in BAECs indicates that L-arginine transport is dissociated from NO generation in these cells.

Animals↗

PubMed1996

Selective induction of a cationic amino acid transporter by tumor necrosis factor-alpha in vascular endothelium.

Treatment of bovine aortic endothelial cells with tumor necrosis factor-alpha (TNF-alpha) resulted in a concentration-dependent increase in L-arginine transport. The stimulatory effect of TNF-alpha was time-dependent, requiring at least 6 hr of exposure. Both actinomycin D and cycloheximide inhibited the TNF-alpha mediated increase in L-arginine transport, indicating that de novo RNA and protein synthesis were required. Ribonuclease protection analysis revealed the presence of cationic amino acid transporter (CAT)-1 and CAT-2 mRNA. Treatment of bovine aortic endothelial cells with TNF-alpha selectively increased the levels of CAT-2 mRNA, whereas message for CAT-1 remained unchanged. These results demonstrate that TNF-alpha stimulates L-arginine transport in endothelial cells by selectively inducing the expression of CAT-2 mRNA. The capacity of TNF-alpha to stimulate the expression of CAT-2 protein may provide an important mechanism by which increases in substrate are provided to endothelial cells during periods of elevated L-arginine metabolism.

Animals↗

PubMed1995

Ethanol potentiates interleukin-1 beta-stimulated inducible nitric oxide synthase expression in cultured vascular smooth muscle cells.

Experiments were performed to examine the effect of ethanol on the production of nitric oxide from interleukin-1 beta (IL-1 beta)-treated cultured rat aortic smooth muscle cells. Incubation of vascular smooth muscle cells with IL-1 beta resulted in the release of nitrite and in the intracellular accumulation of L-citrulline. In parallel with this, IL-1 beta increased inducible nitric oxide synthase (iNOS) mRNA and protein. Ethanol (6.5-650 mM) potentiated the IL-1 beta-mediated stimulation of iNOS mRNA production, the appearance of iNOS protein and the generation of nitrite and L-citrulline from smooth muscle cells in a concentration-dependent manner. In the absence of IL-1 beta, ethanol failed to induce iNOS expression. These results demonstrate that pharmacologically relevant concentrations of ethanol enhance the IL-1 beta-induced expression of the iNOS gene in vascular smooth muscle. The ability of ethanol to augment the release of the platelet inhibitor and vasodilator nitric oxide may, in part, contribute to the beneficial cardiovascular effects associated with moderate alcohol consumption.

Amino Acid Oxidoreductases↗

PubMed1995

Vascular smooth muscle cell heme oxygenases generate guanylyl cyclase-stimulatory carbon monoxide.

BACKGROUND: Carbon monoxide (CO), like nitric oxide (NO), stimulates soluble guanylyl cyclase and thereby raises intracellular levels of cGMP. We examined the endogenous capacity of vascular smooth muscle cells (SMCs) to produce CO from heme through the activity of heme oxygenases. METHODS AND RESULTS: Cultured SMCs from rat aorta (RASMCs) expressed immunoreactive inducible heme oxygenase-1 (HO-1) and constitutive HO-2. Treatment of RASMCs with hemin and sodium arsenite, which are inducers of HO-1, stimulated RASMC cGMP without stimulating nitrite release or inducible NO synthase expression, and the induced elevations of cGMP were not inhibited by the NO synthase inhibitor NG-methyl-L-arginine. Induced CO from RASMCs likewise caused elevation of cGMP levels in platelets coincubated with the vascular cells. Zinc protoporphyrin IX, an inhibitor of HO, reversed the inducible increases in platelet cGMP. CONCLUSIONS: These results indicate that vascular SMCs have both constitutive and inducible HO activity, and they respond to specific stimuli to generate guanylyl cyclase-stimulatory CO in the same SMCs and in coincubated platelets.

Animals↗

PubMed1995

Differential regulation of L-arginine transport and inducible NOS in cultured vascular smooth muscle cells.

Experiments were performed to characterize the uptake of L-arginine in rat aortic smooth muscle cells (SMC) and to examine whether inducers of nitric oxide synthase (NOS) could regulate the transport of L-arginine into these cells. L-Arginine transport by SMC was saturable, Na+ independent, strongly inhibited in the presence of other cationic amino acids, and could be stimulated by preloading the cells with cationic amino acids. Kinetic studies revealed the presence of both a high [Michaelis constant (Km) approximately 125 microM] and low (Km approximately 1.4 mM) affinity L-arginine transporter. Treatment of vascular SMC with interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) resulted in parallel increases in L-arginine transport and nitric oxide (NO) synthesis, as measured by nitrite production. Increasing the concentration of IL-1 beta and TNF-alpha caused a progressive elevation in nitrite production but did not further stimulate L-arginine uptake. Treatment of SMC with the combination of TNF-alpha and interferon-gamma (IFN-gamma) synergistically enhanced nitrite release without having any additional effect on L-arginine transport. Both induction of L-arginine transport and NOS activity by these cytokines were blocked by cycloheximide. Finally, treatment of SMC with interferon-gamma and N6,2'-O-dibutyryl adenosine 3',5'-cyclic monophosphate selectively stimulated the formation of nitrite by SMC but had no effect on L-arginine transport. These results demonstrate that L-arginine transport by cultured vascular SMC is mediated by the system y+ carrier and that inducers of NOS differentially regulate the activity of this transporter.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗

PubMed1994

Cyclic nucleotide regulation of interleukin-1 beta induced nitric oxide synthase expression in vascular smooth muscle cells.

Experiments were performed to examine the effect of cyclic nucleotides on the expression of inducible nitric oxide synthase (iNOS) activity by interleukin-1 beta (IL-1 beta) treated rat aortic smooth muscle cells (SMC). Treatment of vascular SMC with IL-1 beta stimulated iNOS mRNA expression and the subsequent release of nitrite, a stable oxidation product of nitric oxide (NO). Similarly, lipophilic analogues of cAMP also induced both iNOS mRNA expression and nitrite release. The addition of IL-1 beta and cAMP derivatives resulted in a synergistic enhancement of both iNOS mRNA production and of nitrite formation. In contrast, lipophilic analogues of cGMP did not induce iNOS expression. The addition of cGMP derivatives modestly increased IL-1 beta-induced SMC nitrite generation without affecting the production of iNOS mRNA. The capacity of cyclic nucleotides to positively modulate the induction of iNOS activity may play an important role in regulating the release of NO in vivo.

Amino Acid Oxidoreductases↗

PubMed1994

Platelets inhibit the induction of nitric oxide synthesis by interleukin-1 beta in vascular smooth muscle cells.

We have investigated the role of platelets in regulating the hemostatic and vasomotor properties of vascular smooth muscle. Experiments were performed to examine the effect of the releasate from activated platelets on the production of nitric oxide from interleukin-1 beta (IL-1 beta)-treated cultured rat aortic smooth muscle cells. Treatment of vascular smooth muscle cells with IL-1 beta resulted in significant accumulation of nitrite in the culture media and in marked elevation of intracellular cyclic guanosine monophosphate (GMP) levels. The releasate from collagen-aggregated platelets blocked the IL-1 beta-mediated production of nitrite and the accumulation of cyclic GMP in smooth muscle cells in a platelet number-dependent manner. In functional assays, the perfusates from columns containing IL-1 beta-treated smooth muscle cells relaxed detector blood vessels without endothelium and the addition of IL-1 beta-treated smooth muscle cells to suspensions of platelets inhibited their thrombin-induced aggregation. The simultaneous treatment of smooth muscle cells with IL-1 beta and the platelet releasate abolished both the vasorelaxing activities of the perfusates and the inhibition of platelet aggregation. Platelet releasates treated with a neutralizing antibody to platelet-derived growth factor (PDGF) failed to block IL-1 beta-induced nitric oxide production by the smooth muscle cells, as measured by both biochemical and functional assays. The platelet releasate from a patient with gray platelet syndrome likewise failed to block IL-1 beta-induced nitrite release by smooth muscle cells. These results demonstrate that platelets downregulate the production of nitric oxide by IL-1 beta-treated vascular smooth muscle cells through the release of PDGF. This effect may represent a novel mechanism by which platelets regulate vasomotor tone and thrombus formation at sites of vascular injury.

Animals↗

PubMed1993

Protein kinase C is activated in platelets subjected to pathological shear stress.

High levels of fluid shear stress at the blood vessel wall directly stimulate von Willebrand factor (vWF)-mediated platelet adhesion and aggregation and thereby contribute to the pathogenesis of arterial thrombosis. We have found that a pathological level of arterial wall shear stress (90 dynes/cm2) induces platelet aggregation that is associated with the phosphorylation of pleckstrin, a M(r) 47,000 protein kinase C substrate (p47). Shear-induced p47 phosphorylation depends entirely on vWF binding to platelet glycoprotein (Gp) Ib and GpIIb-IIIa, and the specific inhibition of protein kinase C with the staurosporine analogue Ro 31-7549 inhibits the full aggregation response to shear. Shear stress-induced platelet p47 phosphorylation occurs independent of any measurable change in diacylglycerol mass or hydrolysis of phosphatidylinositol 4,5-bisphosphate. These results indicate that mechanical shear stress induces vWF to bind to platelet GpIb and GpIIb-IIIa, stimulating a diacylglycerol-independent pathway of protein kinase C activation that contributes to platelet aggregation in response to shear.

Blood Platelets↗

PubMed1993

Thrombin inhibits induction of nitric oxide synthase in vascular smooth muscle cells.

Experiments were designed to examine whether thrombin affects the production of nitric oxide-like factor(s) evoked by interleukin-1 beta (IL-1 beta) in cultured smooth muscle cells from the rat aorta. IL-1 beta stimulated the release of nitrite (a stable oxidation product of nitric oxide) from cultured smooth muscle cells. Thrombin inhibited in a concentration-dependent manner the release of nitrite caused by IL-1 beta. The inhibition was prevented by hirudin (a thrombin inhibitor) and required the presence of thrombin before or during the induction period. Under bioassay conditions, the perfusates from columns containing IL-1 beta-treated smooth muscle cells relaxed detector rat aortic rings without endothelium. The addition of IL-1 beta-treated smooth muscle cells to suspensions of indomethacin-treated platelets inhibited their aggregation. Control untreated smooth muscle cells or cells treated with thrombin alone did not have such effects. The treatment of smooth muscle cells with IL-1 beta in combination with thrombin blunted both the relaxing activities of the perfusates under bioassay conditions and the inhibition of platelet aggregation. These observations indicate that thrombin inhibits the production of nitric oxide-like factor(s) evoked by the inducible nitric oxide synthase in cultured smooth muscle cells from rat aorta.

Amino Acid Oxidoreductases↗

PubMed1993

Plasmin potentiates induction of nitric oxide synthesis by interleukin-1 beta in vascular smooth muscle cells.

Experiments were performed to examine the effect of the major fibrinolytic protease, plasmin, on the production of nitric oxide from interleukin-1 beta (IL-1 beta)-treated cultured human and rat aortic smooth muscle cells. Incubation of vascular smooth muscle cells with IL-1 beta resulted in significant accumulation of nitrite and nitrate in the culture media. Plasmin, either added exogenously or generated by the reaction of tissue plasminogen activator with plasminogen, potentiated the IL-1 beta-mediated release of nitrite and nitrate from smooth muscle cells in a concentration-dependent manner, without affecting the production of nitrite and nitrate from cells untreated with IL-1 beta. This potentiating effect was abolished when plasmin was incubated with the protease inhibitor, alpha 2-antiplasmin. The perfusates from columns containing IL-1 beta-treated smooth muscle cells relaxed detector blood vessels without endothelium, and the addition of IL-1 beta-treated smooth muscle cells to suspensions of indomethacin-treated platelets inhibited their aggregation. Untreated smooth muscle cells or cells treated with plasmin alone did not have such effects. However, the simultaneous treatment of smooth muscle cells with IL-1 beta and plasmin markedly enhanced both the relaxing activities of the perfusates and the inhibition of platelet aggregation. Treatment of smooth muscle cells with NG-nitro-L-arginine inhibited the cytokine-mediated effects as well as the potentiating effect of plasmin. These results demonstrate that the plasmin can enhance the production of nitric oxide by IL-1 beta-treated vascular smooth muscle cells.

Animals↗

PubMed1993

Cellular basis for the negative inotropic effects of tumor necrosis factor-alpha in the adult mammalian heart.

To define the mechanism(s) responsible for the negative inotropic effects of tumor necrosis factor-alpha (TNF alpha) in the adult heart, we examined the functional effects of TNF alpha in the intact left ventricle and the isolated adult cardiac myocyte. Studies in both the ventricle and the isolated adult cardiac myocyte showed that TNF alpha exerted a concentration- and time-dependent negative inotropic effect that was fully reversible upon removal of this cytokine. Further, treatment with a neutralizing anti-TNF alpha antibody prevented the negative inotropic effects of TNF alpha in isolated myocytes. A cellular basis for the above findings was provided by studies which showed that treatment with TNF alpha resulted in decreased levels of peak intracellular calcium during the systolic contraction sequence; moreover, these findings did not appear to be secondary to alterations in the electrophysiological properties of the cardiac myocyte. Further studies showed that increased levels of nitric oxide, de novo protein synthesis, and metabolites of the arachidonic acid pathway were unlikely to be responsible for the TNF alpha-induced abnormalities in contractile function. Thus, these studies constitute the initial demonstration that the negative inotropic effects of TNF alpha are the direct result of alterations in intracellular calcium homeostasis in the adult cardiac myocyte.

Animals↗

PubMed1992

The induction of nitric oxide synthase activity is inhibited by TGF-beta 1, PDGFAB and PDGFBB in vascular smooth muscle cells.

The effect of transforming growth factor-beta 1 (TGF-beta 1) and platelet-derived growth factor (PDGF) was investigated on the induction of nitric oxide synthase activity caused by interleukin-1 beta in cultured smooth muscle cells from rat aorta. TGF-beta 1, PDGFAB and PDGFBB but not PDGFAA inhibited in a concentration-dependent manner the production of nitrite, an oxidation product of nitric oxide, evoked by interleukin-1 beta. The growth factors alone did not stimulate the release of nitrite. The addition of interleukin-1 beta-treated smooth muscle cells to suspensions of indomethacin-treated human washed platelets inhibited the aggregation evoked by thrombin whereas no effect was observed with untreated cells. Platelet aggregation was not inhibited by smooth muscle cells that had been pretreated with interleukin-1 beta in combination with either TGF-beta 1, PDGFAB or PDGFBB but not with PDGFAA. These observations demonstrate that platelet-derived products such as TGF-beta and PDGFs inhibit the induction of nitric oxide synthase activity in vascular smooth muscle cells.

Amino Acid Oxidoreductases↗

PubMed1992

Endothelium-derived relaxing factor inhibits thrombin-induced platelet aggregation by inhibiting platelet phospholipase C.

Endothelium-derived relaxing factor (EDRF) inhibits platelet function, but the mechanism underlying this inhibitory effect is not known. To examine this, cultured acetylsalicylic acid (ASA)-treated endothelial cells (EC) from bovine aorta (BAEC) or from human umbilical vein (HUVEC) were incubated with washed, ASA-treated human platelets. Incubation of platelets with either BAEC or HUVEC resulted in inhibition of thrombin-induced platelet aggregation that was dependent on the number of EC added. This effect was potentiated by superoxide dismutase and reversed by treating EC with NG-nitro-L-arginine or by treating platelets with methylene blue, indicating that the inhibition of platelet aggregation was due to the release of EDRF by EC. EC significantly blocked the thrombin stimulated breakdown of phosphatidylinositol-4,5-bisphosphate (PIP2) and the production of phosphatidic acid in [32P]orthophosphate-labeled platelets and of inositol trisphosphate in [3H]myoinositol-labeled platelets. In addition, the thrombin-mediated activation of protein kinase C (PKC) and phosphorylation of myosin light chain were inhibited in the presence of EC. Finally, thrombin stimulated an increase in cytosolic ionized calcium concentration ([Ca2+]i) in fura2-loaded platelets that was abolished by concentrations of EC which also blocked thrombin-induced aggregation. These data indicate that EDRF blocks thrombin-induced platelet aggregation by inhibiting the activation of PIP2-specific phospholipase C and thereby suppressing the consequent activation of PKC and the mobilization of [Ca2+]i.

Animals↗

PubMed1991

Platelet inhibition by an L-arginine-derived substance released by IL-1 beta-treated vascular smooth muscle cells.

Experiments were performed to examine whether stimulation of cultured vascular smooth muscle cells by interleukin (IL)-1 beta would induce platelet inhibitory properties of these cells. Incubation of platelets with untreated rat aortic smooth muscle cells had no effect on thrombin-induced platelet aggregation. In contrast, incubation of platelets with IL-1 beta-pretreated smooth muscle cells or the perfusate from such cells resulted in the inhibition of thrombin-induced platelet aggregation. This effect was potentiated by superoxide dismutase and reversed by incubating the IL-1 beta-treated smooth muscle cells with NG-nitro-L-arginine (L-NNA) or by treating the platelets with methylene blue. Cytokine-treated smooth muscle cells inhibited thrombin-stimulated changes in platelet cytosolic ionized calcium, whereas untreated cells were without effect. Incubating platelets with IL-1 beta-treated smooth muscle cells resulted in a 10-fold increase in platelet guanosine 3',5'-cyclic monophosphate (cGMP) levels, whereas untreated smooth muscle cells had no effect. The elevation of platelet cGMP induced by the IL-1 beta-treated smooth muscle cells was prevented by exposing the cytokine-treated cells to L-NNA or by treating platelets with methylene blue. Treatment of smooth muscle cells with IL-1 beta also resulted in an eightfold increase in nitrite production, which was blocked when the cells were incubated with L-NNA. The addition of cycloheximide to smooth muscle cells during their incubation with IL-1 beta completely inhibited smooth muscle cell nitrite production, the effects of the smooth muscle cells on platelet cGMP levels, and platelet responses to thrombin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Altered myocardial prostaglandin synthesis in spontaneously diabetic rats.

Patients with diabetes mellitus have an increased susceptibility to heart disease. The exact mechanism for this phenomenon is unclear. Abnormalities in prostaglandin (PG) production have been suggested as a possible cause. In this connection, we examined the PG synthetic capacity of cardiac microsomes from spontaneously diabetic rats. Cardiac microsomes from diabetic and control rats produced varying amounts of 6-keto-PGF1 alpha (stable degradation product of PGI2), PGE2, PGD2, PGF2 alpha, and TXB2 (stable breakdown product of TXA2). In both instances the production of 6-keto-PGF1 alpha predominated, however, microsomes from diabetic rats showed markedly greater conversion of arachidonic acid to all the PG products, especially 6-keto-PGF1 alpha. When PGF2 alpha metabolism was detected between diabetic and control heart preparations. These results show an enhanced cyclooxygenase activity in diabetic rat hearts without any change in prostaglandin dehydrogenase activity. Such a change may promote some of the cardiac alterations seen in diabetic mellitus.

Animals↗

PubMed1989

Effect of diabetes on metabolic coronary dilatation in the rat.

There is increasing evidence that patients with diabetes mellitus are prone to ischaemic heart disease. This study examined cardiac hyperactivity and its consequent metabolically induced coronary dilatation in isolated, perfused, electrically paced rat hearts from control and spontaneously diabetic Bio-Breeding (BB) rats. Cardiostimulation produced by noradrenaline, calcium, or by tachycardia elicited increases in coronary flow that were significantly lower in diabetic hearts. However, the inotropic responses to noradrenaline and calcium in diabetic preparations were comparable to control. When coronary vascular reactivity was tested with sodium nitroprusside and adenosine, a decreased dilator response was observed with adenosine in diabetic hearts while no difference was observed with sodium nitroprusside. It is suggested that failure in the adaptive coronary flow response to cardiac hyperactivity in diabetes may, in part, be responsible for the higher incidence of ischaemic heart disease in the diabetic population.

Adenosine↗