Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.26.9 (ribonuclease)
 6,589 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An autopsy case of mixed connective tissue disease (MCTD) with pulmonary hypertension is presented. A 34-year-old woman suffering from arthralgia, Raynaud's phenomenon, and dyspnea of 6-years duration was diagnosed as having MCTD on the basis of a high titer (1:160,000) of serum antibody to the ribonuclease-sensitive component of extractable nuclear antigen. Examination of cardiac function revealed the complication of pulmonary hypertension. Autopsy revealed concentric intimal cellular proliferation of the small arteries and arterioles of both lungs. Typical plexiform lesions of these vessels were also observed. These findings coincide with those of plexogenic pulmonary angiopathy of primary pulmonary hypertension (PPH). This is the second autopsy case of MCTD with fatal pulmonary hypertension reported and our observations suggest that some cases with PPH who had immunological abnormalities but could not be classified as cases of classical collagen disease, may have been induced by MCTD.
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PMID:Mixed connective tissue disease with fatal pulmonary hypertension. 715 44

The canine model of pacing-induced heart failure (HF) simulates human dilated cardiomyopathy and is characterized by severe hemodynamic perturbations. We have previously demonstrated increased plasma endothelin-1 (ET-1) and left ventricular (LV) tissue peptide levels in this model. However, the gene expression of ET-1 has not been studied. Accordingly, we compared preproET-1 mRNA in the lungs and LV in control normal dogs, dogs with severe HF after 3 weeks of rapid pacing (pHF), and pHF dogs chronically treated with an ETA antagonist, LU135252 (pHF-LU). PreproET-1 mRNA expression was determined by ribonuclease protection assay and quantified by densitometry. In paced dogs, mean pulmonary artery pressure (PA) and LV end-diastolic pressure (LVEDP) increased markedly from 16 +/- 4 and 8 +/- 3 mm Hg, respectively, at baseline to 40 +/- 11 and 34 +/- 7 mm Hg, respectively, at 3 weeks (both p < 0.001). Treatment with LU135252 attenuated the increase in PA and LVEDP by 30% and 19%, respectively (p < 0.05 for both). Compared to controls, preproET-1 mRNA expression in the LV and lungs was markedly increased in pHF. This was not changed in the LV but was reduced in the lungs by treatment with the ETA antagonist. Increased pulmonary and LV expression of preproET-1 suggests that ET-1 plays a role in mediating the pulmonary hypertension and LV dysfunction characteristic of this model.
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PMID:Increased cardiac and pulmonary endothelin-1 mRNA expression in canine pacing-induced heart failure. 959 2

Previous studies suggest that inducible (i) nitric oxide synthase (NOS) expression within the pulmonary vasculature is increased in rats with chronic hypoxia (CH)-induced pulmonary hypertension. We therefore hypothesized that enhanced iNOS expression associated with CH causes attenuated pulmonary vasoconstrictor responsiveness. To test this hypothesis, we examined the effect of selective iNOS blockade with L-N6-(1-iminoethyl)lysine dihydrochloride (L-NIL) and nonselective NOS inhibition with Nomega-nitro-L-arginine (L-NNA) on vasoconstrictor responses to U-46619 in isolated saline-perfused lungs from both control and CH (4 wk at 380 mmHg) rats. We additionally measured pulmonary hemodynamic responses to L-NIL in conscious CH rats (fraction of inspired O2 = 0.12). Finally, iNOS mRNA levels were assessed in lungs from each group of rats using ribonuclease protection assays. Despite a significant increase in iNOS mRNA expression after exposure to CH, responses to U-46619 were unaltered by L-NIL but augmented by L-NNA in lungs from both control and CH rats. Pulmonary hemodynamics were similarly unaltered by L-NIL in conscious CH rats. We conclude that iNOS does not modulate pulmonary vasoconstrictor responsiveness after long-term hypoxic exposure.
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PMID:Unaltered vasoconstrictor responsiveness after iNOS inhibition in lungs from chronically hypoxic rats. 988 64

Natriuretic peptides (NPs), such as atrial natriuretic peptide (ANP), C-type natriuretic peptide (CNP), and adrenomedullin (ADM), are endogenous vasodilators acting via specific receptors. This study addressed the question of how pulmonary artery (PA) responses to these peptides and the gene expression of their receptors are modulated in pulmonary hypertension rat models exposed to chronic hypoxia. In this study, isometric tension was measured in PA rings exposed to these NPs and 8-bromoguanosine 3', 5'-cyclic monophosphate (8-bromo-cGMP). It was compared with messenger ribonucleic acid (mRNA) levels of NP-A and -B receptors, which bind to ANP and CNP, respectively, as determined by ribonuclease (RNase) protection assay. Chronic hypoxia increased the maximal relaxation elicited by ANP, but the responses to CNP and 8-bromo-cGMP were unchanged. Chronic hypoxia did not change NP-A and -B receptor mRNA levels. The results showed that pulmonary artery response to atrial natriuretic peptide is selectively enhanced, possibly via a post-transcriptional modulation of its receptor in chronically hypoxia rats. These pharmacological characteristics of atrial natriuretic peptide are consistent with the hypothesis that the atrial natriuretic peptide system is protective against the progression of pulmonary hypertension.
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PMID:Modulated vasodilator responses to natriuretic peptides in rats exposed to chronic hypoxia. 1070 11

Monocrotaline-induced pulmonary hypertension (PH) in rats is preceded by an inflammatory response in the lungs, and interleukin-6 (IL-6) is expressed in response to inflammation. To evaluate the role of IL-6 in monocrotaline-induced PH, rats received a single subcutaneous injection of monocrotaline (60 mg/kg) or an equivalent amount of normal saline. Pulmonary artery pressure (Ppa), right ventricular hypertrophy (RVH), expression of IL-6 mRNA, and bioactivity of IL-6 in the lungs of these rats were examined 48 hours and 1 and 2 weeks after administration of monocrotaline. The effects of dexamethasone treatment on monocrotaline-induced PH also were evaluated. Two weeks after administration of monocrotaline, significant PH and RVH developed in these rats. Reverse transcription-polymerase chain reaction (RT-PCR) revealed expression of IL-6 mRNA in the lungs 48 hours and 1 and 2 weeks after administration of monocrotaline. This was confirmed using ribonuclease protection assay. The bioactivity of IL-6 in lung extracts progressively increased. Dexamethasone markedly inhibited expression of IL-6 mRNA and IL-6 bioactivity in the lungs, with concomitant attenuation of monocrotaline-induced PH and RVH. Our data show that monocrotaline induces expression of IL-6 mRNA in rat lungs and that inhibition of IL-6 results in attenuation of PH. These findings indicate that IL-6 may play a role in the pathogenesis of PH.
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PMID:Monocrotaline induces interleukin-6 mRNA expression in rat lungs. 1172 Jun 14

Pulmonary hypertension associated with human immunodeficiency virus (HIV) infection also involves injury to the lung endothelium. However, the pathogenesis of HIV-induced pulmonary hypertension is not known; we hypothesized that HIV or secreted viral proteins could play a role in vascular injury and the increased frequency of pulmonary hypertension observed in HIV-infected patients. Here, we report that exposure of HIV-1 gp120 proteins to primary human lung microvascular endothelial cells causes apoptosis, as assessed by TUNEL assay, Annexin-V staining, and DNA laddering. Using ribonuclease protection assay and Western blotting we find that gp120-induced apoptosis of lung endothelial cells involves a down-regulation in Bcl-xl mRNA and proteins. In addition, gp120 significantly increases secretion of the potent vasoconstrictor endothelin-1 by human lung endothelial cells. These data suggest that secreted HIV gp120 proteins induce lung endothelial cell injury and could contribute to the development of HIV-associated pulmonary hypertension.
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PMID:Induction of apoptosis and endothelin-1 secretion in primary human lung endothelial cells by HIV-1 gp120 proteins. 1597 50