Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

After addition of exogenous human renin, the in vitro rate of angiotensin I generation is faster in plasma of patients with chronic renal insufficiency and, to a lesser extent, in plasma of patients with essential hypertension than in plasma from normotensive control subjects. The increased reactivity of renin in hypertensive and uremic plasma is not related to differences of endogenous renin activity, angiotensinase activity, renin substrate concentration, or substrate reactivity. Addition of normal, hypertensive, and uremic plasma to a human renin-sheep renin substrate system inhibited the rate of angiotensin generation, although significantly less inhibition was observed with uremic plasma. The reactivity of renin increased in normal plasma but not in uremic plasma after treatment with 95% acetone. After acetone extraction renin reactivity in normal and plasma inhibited the rate of angiotensin generation in a renin-renin substrate system. Less inhibition occurred with the acetone extract from a pool of uremic plasma. These results provide evidence for the existence of a naturally occurring acetone soluble renin inhibiting factor in normal and uremic plasma. The increased reactivity of renin in uremic plasma may be related to a deficiency of this factor.
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PMID:Evidence for the existence of an acetone soluble renin inhibiting factor in normal human plasma. 113 76

Brain renin-angiotensin system hyperactivity has been implicated in the development and maintenance of hypertension. We reported previously in the brain that aminopeptidase A and aminopeptidase N are involved in the metabolism of angiotensin II and angiotensin III, respectively. By using in vivo specific and selective aminopeptidase A and aminopeptidase N inhibitors, we showed that angiotensin III is one of the main effector peptides of the brain renin-angiotensin system, exerting a tonic stimulatory control more than blood pressure in hypertensive rats. Aminopeptidase A, the enzyme generating brain angiotensin III, thus represents a potential target for the treatment of hypertension. We demonstrated here the antihypertensive effects of RB150, a prodrug of the specific and selective aminopeptidase A inhibitor, EC33, in spontaneously hypertensive rats, a model of human essential hypertension. Oral administration of RB150 in conscious spontaneously hypertensive rats inhibited brain aminopeptidase A activity, demonstrating the central bioavailability of RB150 and its ability to generate EC33 into the brain. Oral RB150 treatment dose-dependently reduced blood pressure in spontaneously hypertensive rats with an ED(50) of 30 mg/kg, lasting for several hours. This decrease in blood pressure is partly attributed to a decrease in sympathetic tone, reducing vascular resistance. This treatment did not modify systemic renin-angiotensin system activity. Concomitant oral administration of RB150 with a systemic renin-angiotensin system blocker, enalapril, potentiated the RB150-induced blood pressure decrease achieved in <2 hours. Thus, RB150 may be the prototype of a new class of centrally active antihypertensive agents that might be used in combination with classic systemic renin-angiotensin system blockers to improve blood pressure control.
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PMID:Central antihypertensive effects of orally active aminopeptidase A inhibitors in spontaneously hypertensive rats. 2271 Jun 44

Aminopeptidase A (APA) cleaves the N-terminal aspartyl acid residue of angiotensin II (Ang II) to produce angiotensin III (Ang III). It has been reported that the APA knockout mouse exhibits elevated blood pressure. Therefore, the APA gene is thought to be a susceptibility gene for essential hypertension (EH). However, extensive studies have yet to define the relationship between the APA gene and EH. The aims of this study were to genotype some of the single nucleotide polymorphisms (SNPs) for the human APA gene and to perform a haplotype-based case-control study to further assess the association between and the APA gene and EH. We performed a genetic association study using SNPs in 227 EH patients and 221 age-matched normotensive (NT) individuals. Although the overall distribution of the genotype did not significantly differ between the EH and NT groups when the entire group of subjects were evaluated, the frequency of rs2290105 did differ between the two when just women were included in the analysis. The haplotype-based case-control analysis also revealed a significant difference between the women of the EH and NT groups. The A-T-A-C haplotype was significantly higher in the EH versus the NT group. These results suggest that rs2290105 and the A-T-A-C haplotype of the APA gene are genetic markers for EH, and that APA or a neighboring gene might be a susceptibility gene for EH.
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PMID:Association study: the aminopeptidase a gene and essential hypertension. 2367 50