Kathleen M. MacLeod

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OBJECTIVE The purpose of the present study was to determine whether increased activation of the RhoA/Rho-kinase (ROCK) pathway occurs in diabetic cardiomyopathy and whether acute inhibition of this pathway improves contractile function of the diabetic heart. METHODS Male Wistar rats were made diabetic with streptozotocin. Twelve to fourteen weeks later,(More)
OBJECTIVE Impaired cardiovascular function in diabetes is partially attributed to pathological overexpression of inducible nitric oxide synthase (iNOS) in cardiovascular tissues. We examined whether the hyperglycemia-induced increased expression of iNOS is protein kinase C-beta(2) (PKCbeta(2)) dependent and whether selective inhibition of PKCbeta reduces(More)
Multiple calcium-binding proteins (CaBPs) are expressed at high levels and in complementary patterns in the auditory pathways of birds, mammals, and other vertebrates, but whether specific members of the CaBP family can be used to identify neuronal subpopulations is unclear. We used double immunofluorescence labeling of calretinin (CR) in combination with(More)
OBJECTIVES The RhoA/ROCK pathway contributes to diabetic cardiomyopathy in part by promoting the sustained activation of PKCβ2 but the details of their interaction are unclear. The purpose of this study was to investigate if over-activation of ROCK in the diabetic heart leads to direct phosphorylation and activation of PKCβ2, and to determine if their(More)
AIMS The presence of metabolic abnormalities such as insulin resistance and elevated levels of various vasoconstrictor G-protein-coupled receptor (GPCR) agonists contributes to the development of hypertension. Recent studies have suggested a link between disease progression and activation of growth factor receptor signalling pathways such as the epidermal(More)
The purpose of this study was to investigate the effect of chronic treatment with prazosin, a selective α1-adrenoceptor antagonist, on the development of hypertension in fructose-fed rats (FFR). High-fructose feeding and treatment with prazosin (1 mg/kg/day via drinking water) were initiated simultaneously in male Wistar rats. Systolic blood pressure,(More)
The ability of the muscarinic agonist, carbachol, to overcome increases in tension and in cAMP produced in response to the adenylate cyclase activator, forskolin, in rabbit papillary muscles was measured. Forskolin alone increased cAMP levels to a much greater extent than did a concentration of isoproterenol that produced an equivalent increase in tension.(More)
Previous studies from this laboratory have demonstrated an enhancement in both the contractile and signaling response to stimulation of either alpha-1 adrenoceptors or guanine nucleotide binding proteins (G proteins) in arteries from male Wistar rats with 12 to 14 weeks of streptozotocin-induced diabetes. The purpose of the present investigation was to(More)
The muscarinic agonist carbachol antagonized positive inotropic responses of rabbit left atria to the beta-adrenoceptor agonist isoproterenol, the adenylate cyclase activator forskolin and the phosphodiesterase inhibitor IBMX. Carbachol also reduced cAMP levels elevated by isoproterenol, but had no significant effect on cAMP levels in the presence of either(More)
SUMMARY Previous studies have suggested that the lnotropic effects of glucagon on the guinea pig heart, but not on the rat heart, could be dissociated from its effects on cyclic AMP formation. We compared the effects of glucagon on working rat and guinea pig hearts to reinvestigate this proposed dissociation. When administered to spontaneously beating(More)
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