المؤلفون: Casselbrant, Anna, 1970, Edebo, Anders, 1968, Wennerblom, Johanna, 1969, Lönroth, Hans, 1952, Helander, Herbert F, 1935, Vieth, M., Lundell, L., Fändriks, Lars, 1956

المصدر: Gastroenterology. 132(1):249-60

مصطلحات موضوعية: MEDICAL AND HEALTH SCIENCES, MEDICIN OCH HÄLSOVETENSKAP, Aged, 80 and over, Angiotensin II/*pharmacology, Angiotensin II Type 1 Receptor Blockers/administration & dosage, Angiotensinogen/genetics, Benzimidazoles/administration & dosage, Esophageal Sphincter, Lower/*physiology, Esophagus/*physiology, Female, Gene Expression, Humans, Male, Manometry, Middle Aged, Muscle Contraction/*drug effects, Peptidyl-Dipeptidase A/genetics, Peristalsis/drug effects, Receptor, Angiotensin, Type 1/genetics/metabolism, Type 2/genetics/metabolism, Renin/genetics/metabolism, Tetrazoles/administration & dosage, Vasoconstrictor Agents/*pharmacology

الوصف: BACKGROUND & AIMS: Angiotensin II is a potent activator of smooth muscles but has not been much investigated with regard to gastrointestinal motor activity. This study explores expression of the renin-angiotensin system (RAS) in human esophageal musculature and actions by Angiotensin II both in vitro and in vivo. METHODS: Muscular specimens of esophageal body and lower esophageal sphincter were obtained from patients undergoing resection as a result of mucosal neoplasm. Healthy volunteers participated in functional examinations of esophageal motility assessed by high-resolution manometry and multiple transmucosal potential-difference measurements. RESULTS: Gene transcripts of key components of RAS were found in the esophageal musculature. Immunohistochemistry revealed a distinct staining for Angiotensin II type 1 (AT(1)) receptors in the muscular bundles and blood-vessel walls, whereas Angiotensin II type 2 receptors were confined to blood vessels only. Angiotensin II caused concentration-dependent contractions in vitro, which were inhibited by the AT(1) receptor antagonist losartan but not by the Angiotensin II type 2 receptor antagonist PD123319. Administration of the AT(1) receptor antagonist candesartan reduced the amplitude of swallow-induced peristaltic contractions and both the length and pressure amplitude of baseline high-pressure zone at the esophagogastric junction. Neither swallow-induced axial movements, nor the contraction after transient lower esophageal sphincter relaxations, were influenced by candesartan pretreatment. CONCLUSIONS: The study demonstrates a local RAS in the musculature of the distal esophagus and that Angiotensin II is a potent stimulator of esophageal contractions via the AT(1) receptor. The results suggest that Angiotensin II participates in the physiological control of the human esophageal motor activity.

الوصول الحر: https://gup.ub.gu.se/publication/47804Test

المؤلفون: Kurland, Lisa, Melhus, Håkan, Sarabi, Mahziar, Millgård, Jonas, Ljunghall, Sverker, Lind, Lars

المصدر: Clinical Physiology. 21(3):343-349

مصطلحات موضوعية: Adult, Aged, Aldosterone Synthase/genetics, Endothelium, Vascular/*physiology, Female, Gene Deletion, Humans, Male, Middle Aged, Nitroprusside/administration & dosage/pharmacology, Peptidyl-Dipeptidase A/*genetics, Polymorphism, Genetic, Restriction Fragment Length, Receptor, Angiotensin, Type 1, Type 2, Receptors, Angiotensin/genetics, Renin-Angiotensin System/*genetics, MEDICINE, MEDICIN

الوصف: BACKGROUND: Our aim was to test the hypothesis that genes encoding components in the renin-angiotensin system influence endothelial vasodilatory function.METHODS: In 59 apparently healthy, normotensive individuals, endothelium-dependent vasodilation (EDV) and endothelial-independent vasodilation (EIDV) was evaluated by infusing metacholine and sodium nitroprusside into the brachial artery. Forearm blood flow was measured by venous occlusion plethysmography. The ACE insertion (I)/deletion (D) polymorphism, the T174M and M235T angiotensinogen restriction fragments length polymorphisms, the angiotensin II receptor type 1 (AT1R) A1166C, and the aldosterone synthase gene (CYP11B2) C-344T polymorphisms were analysed.RESULTS: When analysing the ACE, the two angiotensinogen and the aldosterone synthase CYP11B2 genotypes independently, no significant association with endothelial vasodilatory function was found. However, a significant reduction in endothelium-dependent vasodilation was observed in the subjects (n=9) with the ACE D allele and the angiotensinogen T174M genotype (P<0.05). Subjects with the AT1R genotype AC showed a reduction in both EDV (P=0.05) and EIDV (P=0.04) when compared with those with the AA genotype.CONCLUSIONS: The subjects with the ACE D allele in combination with the angiotensinogen T174M genotype are associated with a reduced EDV. This together with the observation that the AC AT1R genotype is associated with a reduction in both EDV and EIDV, supports the hypothesis that endothelial vasodilatory function is influenced by genes in the renin-angiotensinogen system.

وصف الملف: print

الوصول الحر: https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-73093Test
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=11380534&dopt=CitationTest

المؤلفون: Kurland, Lisa, Melhus, Håkan, Karlsson, Julia, Kahan, Thomas, Malmqvist, Karin, Öhman, K. Peter, Nyström, Fredrik, Hägg, Anders, Lind, Lars

المصدر: Journal of Hypertension. 19(10):1783-1787

مصطلحات موضوعية: Adrenergic beta-Antagonists/therapeutic use, Antihypertensive Agents/*therapeutic use, Atenolol/therapeutic use, Biphenyl Compounds/*therapeutic use, Blood Pressure/*drug effects, Double-Blind Method, Female, Forecasting, Humans, Hypertension/*drug therapy/*genetics, Male, Middle Aged, Peptidyl-Dipeptidase A/*genetics, Polymorphism, Genetic/*physiology, Receptor, Angiotensin, Type 1, Receptors, Angiotensin/*antagonists & inhibitors, Research Support, Non-U.S. Gov't, Tetrazoles/*therapeutic use, Treatment Outcome, MEDICINE, MEDICIN

الوصف: OBJECTIVES: To determine whether polymorphisms in the renin-angiotensin system can predict blood pressure-lowering response to antihypertensive treatment; more specifically, in response to treatment with irbesartan or atenolol. DESIGN AND METHODS: Eighty-six patients with hypertension were randomized to double-blind treatment with either the angiotensin II type 1 receptor antagonist irbesartan or the beta1 adrenergic receptor blocker atenolol and followed for 3 months. We analysed angiotensinogen T174M and M235T, angiotensin converting enzyme (ACE) I/D and angiotensin II type 1 receptor A1166C polymorphisms and related them to blood pressure reduction. RESULTS: The mean reductions in blood pressure were similar for both treatments. In the irbesartan group, individuals homozygous for the ACE gene I allele showed a greater reduction in diastolic blood pressure, exceeding those with the D allele (-18 +/- 11 SD versus -7 +/- 10 mmHg, P = 0.0096). This was not the case during treatment with atenolol, and the interaction term between type of treatment and ACE II genotype was significant (P = 0.0176). The angiotensinogen and angiotensin II type 1 receptor polymorhisms were not related to the response to treatment. CONCLUSIONS: ACE genotyping predicted the blood pressure-lowering response to antihypertensive treatment with irbesartan but not atenolol. Thus, specific genotypes might predict the response to specific antihypertensive treatment.

وصف الملف: print

الوصول الحر: https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-73122Test
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=11593098&dopt=CitationTest