The American journal of physiology
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Comparative Study
Effect of intrahypothalamic insulin on sympathetic nervous function in rats drinking a high-sucrose solution.
Hyperinsulinemia has been associated with increased sympathetic nervous activity. However, direct injection of insulin into the hypothalamus of anesthetized rats produces sympatho-inhibition. This discrepancy could be due to confounding effects of anesthesia or insulin resistance on central neural function. ⋯ Drinking a 10% sucrose solution enhanced the sympathoexcitatory effect of insulin in the urethan-anesthetized rats but had no effect in the other two groups. The sucrose solution did not affect insulin sensitivity in any group; however, urethan anesthesia did produce insulin resistance. These data show that central effects of insulin are sensitive to anesthesia and do not support a sympathoexcitatory role for insulin in the ventromedial hypothalamus of conscious rats, at least in relation to the renal sympathetic nerves.
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Comparative Study
Calcitonin gene-related peptide promotes cerebrovascular dilation during cortical spreading depression in rabbits.
We examined the role of calcitonin gene-related peptide (CGRP) in cortical spreading depression (CSD)-induced dilation of rabbit pial arterioles. In urethan-anesthetized rabbits instrumented with a closed cranial window, CSD induction with KCl dilated pial arterioles from 86 +/- 10 to 132 +/- 13 (mean +/- SE, n = 6) microns (a 54 +/- 9% increase). Topical administration of 12.8 microM CGRP-(8-37), a competitive inhibitor of the CGRP receptor, reduced CSD-induced pial dilation from 54 +/- 9% baseline to 33 +/- 9% (P < 0.05). ⋯ We also evaluated the dilator potency of substance P (SP) compared with CGRP. Dilation with 10(-7) M SP was only 22 +/- 11%, whereas arterioles dilated to 57 +/- 7% above baseline diameter with 10(-7) M CGRP. We conclude that CGRP contributes to the transient arteriolar dilation that is characteristic of CSD.
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Matrix metalloproteinases (MMPs) and elastase are proteolytic enzymes specifically directed against extracellular matrix (ECM) components. They are secreted by inflammatory cells and may consequently contribute to the lesions of the ECM observed during acute pulmonary edema. We therefore evaluated the MMP and elastase activities, which are secreted by cultured alveolar macrophages (AMACs) and polymorphonuclear neutrophils (PMNs) and present in the bronchoalveolar lavage (BAL) fluid in a guinea pig model of acute lung injury induced by intratracheal instillation of lipopolysaccharide (LPS). ⋯ The 92-kDa gelatinase was secreted by both AMACs and PMNs, as demonstrated by zymography of their respective culture media. When tested on [3H]elastin, the elastase activity of BAL fluid of LPS-treated animals exhibited no increase, but when tested on a synthetic peptidic substrate [N-succinyl-(L-alanine)3-p-nitro anilide (SLAPN)], increased elastase-like activity was observed (from 17 +/- 4 nmol of SLAPN.200 microliters BAL fluid-1.24 h-1 in control group to 34 +/- 8 in LPS group, P < 0.05). This increase was attributable to the activity of a metalloendopeptidase that was inhibited by the metal chelator EDTA but not by the specific tissue inhibitor of MMPs.
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We studied the effect of nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor, on the increases in cerebral blood flow (CBF) elicited by stepwise elevations in arterial partial pressure of CO2 (PaCO2) from normocapnia up to 204 mmHg. Rats were anesthetized with halothane and ventilated. CBF was monitored over the parietal cortex using a laser-Doppler flowmeter. ⋯ Reduction of resting CBF (-50 +/- 4%; n = 6) by administration of chloralose (20-40 mg/kg i.v.) did not attenuate the CBF response to hypercapnia (P > 0.05). We also found that the attenuation by L-NAME of resting CBF (n = 5) and of the cerebrovasodilation elicited by hypercapnia (n = 6) has a relatively slow time course, the effects reaching a maximum 45-60 min after intravenous administration of the drug. We conclude that L-NAME does not attenuate the CBF response to CO2 uniformly at all levels of hypercapnia.(ABSTRACT TRUNCATED AT 250 WORDS)
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The immunocytochemical detection of Fos, the protein product of the immediate-early gene c-fos, was used as a marker for activated neurons to examine whether the C1 neurons in the rat rostral ventrolateral medulla (RVLM) respond to changes in baroreceptor afferent activity. After hydralazine-induced hypotension or sinoaortic denervation, two treatments that reduce baroreceptor afferent activity, numerous Fos-positive neurons were observed in the RVLM. ⋯ Furthermore, in hydralazine-treated rats, the majority of Fluorogold-labeled Fos-positive neurons contained PNMT. These results suggest that C1 neurons are sensitive to baroreceptor afferent input and support a role of these neurons in cardiovascular regulation.