Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human aspartic proteinases include pepsinogen A, pepsinogen C, cathepsin D, cathepsin E and renin. Comparative analysis of the proteinase genes reveals a high degree of similarity with regard to their respective coding sequences and the location of exon-intron junctions. Despite strong conservation of the regions containing the active site aspartyl groups, genetic polymorphisms have been identified for each of the proteinase genes with the exception of cathepsin D. These genetic polymorphisms are useful for localization of genes on linkage maps as well as determination of gene copy number. The chromosomal location of each aspartyl proteinase has been determined by a variety of gene mapping methods employing recombinant DNA probes including; analysis of somatic cell hybrid mapping panels, in situ hybridization to metaphase chromosome preparations and family linkage analysis with polymorphic markers. Pepsinogen A exhibits the most extensive polymorphism among aspartic proteinases which can be detected by either by protein electrophoresis or by DNA analysis. Southern blot hybridization with respective DNA probes and polymerase chain reaction (PCR) amplification have revealed nucleotide differences located within the coding and noncoding portions of the aspartic proteinase genes. These polymorphisms can be used to investigate potential roles of each proteinase in genetically influenced clinical conditions. The development of additional highly polymorphic markers detected by PCR amplification of divergent nucleotide sequence repeats will greatly assist with documentation of the effect of genetic variation of the aspartic proteinases may have in specific clinical diseases such as ulcer and hypertension.
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PMID:Genetic variation of human aspartic proteinases. 145 73

Controversy exists whether vascular smooth muscle cells in vivo synthesize renin, thereby providing a critical component of the hypothesized vascular renin-angiotensin system. To examine this question, we enzymatically isolated and pooled the medial layer of thoracic aortas from Sprague-Dawley rats that were either untreated or enalapril treated for 3 days, isolated messenger RNA (mRNA), and performed Northern blot analysis with rat complementary DNA (cDNA) probes for renin, cathepsin D, and cathepsin E. Renin mRNA was detected in kidney but was not detected in aortic smooth muscle from the untreated or enalapril-treated groups. Cathepsin E mRNA was detected in enalapril-treated aorta and kidney, and cathepsin D mRNA was detected in all tissues examined. cDNA was synthesized and subjected to polymerase chain reaction analysis by using primers corresponding in sequence to regions conserved throughout the aspartic proteinases. Cathepsins D and E were amplified from kidney and aortic cDNA. Renin was less consistently amplified from the aortic cDNA and was much less abundant than cathepsin E or cathepsin D. These results suggest that 1) renin mRNA is present in aortic smooth muscle cells in vivo in quantities detectable only after multiple rounds of polymerase chain reaction amplification, 2) renin mRNA is not upregulated in aortic smooth muscle after converting enzyme inhibition, and 3) cathepsins D and E are the predominant aspartic proteinases in aortic smooth muscle.
Hypertension 1992 Jun
PMID:Polymerase chain reaction analysis of renin in rat aortic smooth muscle. 159 70

In the present paper we report the results of a study in which we compared 2 different approaches to the computation of biological age (BA) in a sample of 322 Japanese men (age range 20 to 79 years). In the first approach, 4 commonly used measures of health-related fitness (VO2peak, trunk flexion from a standing position, body fat, and grip strength) were reduced to a single BA score (HRF Age) using principal component analysis. In contrast, in the second approach, 3 commonly used measures of skilled motor performance and agility (vertical jump, stepping side-to-side, and balancing on one leg with eyes closed) were reduced to a single BA score (SMP Age) using similar multivariate procedures. The criterion-related validity of both of the BA measures was examined by assessing each measure's ability to discriminate between healthy and active groups of subjects. This was achieved by classifying the original subject pool into regularly active (ACT; n = 108) and healthy (HLTH; n = 169) subgroups on the basis of self-reported activity levels. Analyses revealed that HRF Age was a more powerful discriminator between the two activity groups than SMP Age. While HRF Age of HLTH subjects was very close to their chronological age (CA), in the ACT group, HRF Age was on average 15 years less than their CA (P < 0.05). In a separate analysis, we assessed the HRF Age of patients with ischemic heart disease, hypertension, obesity, or diabetes (PAT; n = 45). The HRF Age of these subjects averaged 10 years above their CA. Our data suggest that commonly used measures of health-related fitness can be usefully employed as indices of BA which differentiate between individuals of similar ages but differing health and physical activity status. In contrast, measures of skilled motor performance were found to be less valuable measures of BA. The implication of our findings for future experimental design in exercise and aging research is discussed.
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PMID:The relative utility of health-related fitness tests and skilled motor performance tests as measures of biological age in Japanese men. 871 21

The purpose of this study was to investigate the effect of EMAP II on free radical state of the heart and blood vessels, to restore cNOS coupling and cardiac hemodynamics in spontaneously hypertensive rats. It was found that, due to the combined inhibition of oxidative and nitrosative stress, EMAP I quickly restores impaired in hypertension constitutive de novo synthesis of NO by restoring cNOS coupling. Restoration by EMAP II of constitutive de novo synthesis NO abolished cardiac and endothelial dysfunction in spontaneously hypertensive rats. In hypertension, the introduction of EMAP II helped to improve the performance of the pumping function of the heart (stroke volume increased by 18.2 %, cardiac output -22 %), an arterial stiffness decreased by 23.2 %, process of relaxation of the left ventricle improved, due to decreased in 4,7 times myocardial end-diastolic stiffness.
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PMID:[ENDOTHELIAL MONOCYTEACTIVATING FACTOR II CANCELS OXIDATIVE STRESS, CONSTITUTIVE NOS UNCOUPLING AND INDUCED VIOLATIONS OF CARDIAC HEMODYNAMICS IN HYPERTENSION (PART II)]. 2649 31

Respiratory airway, blood vessel and intestinal wall remodeling, in which smooth muscle remodeling plays a major role, is a key pathological event underlying the development of several associated diseases, including asthma, cardiovascular disorders (e.g., atherosclerosis, hypertension, and aneurism formation), and inflammatory bowel disease. However, the mechanisms underlying these remodeling processes remain poorly understood. We hypothesize that the creation of chronic inflammation-mediated networks that support and exacerbate the airway, as well as vascular and intestinal wall remodeling, is a crucial pathogenic mechanism governing the development of the associated diseases. The failed inflammation resolution might be one of the causal pathogenic mechanisms. Hence, it is reasonable to assume that applying specialized, pro-resolving mediators (SPMs), acting via cognate G-protein coupled receptors (GPCRs), could potentially be an effective pathway for treating these disorders. However, several obstacles, such as poor understanding of the SPM/receptor signaling pathways, SMP rapid inactivation as well as their complex and costly synthesis, limit their translational potential. In this connection, stable, small-molecule SPM mimetics and receptor agonists have emerged as new, potentially suitable drugs. It has been recently shown in preclinical studies that they can effectively attenuate the manifestations of asthma, atherosclerosis and Crohn's disease. Remarkably, some biased SPM receptor agonists, which cause a signaling response in the desired inflammation pro-resolving direction, revealed similar beneficial effects. These encouraging observations suggest that SPM mimetics and receptor agonists can be applied as a novel approach for the treatment of various chronic inflammation conditions, including airway, vascular and intestinal wall remodeling-associated disorders.
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PMID:Receptors for pro-resolving mediators as a therapeutic tool for smooth muscle remodeling-associated disorders. 3327 3