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)

When 3H-proline was administered to spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats, its incorporation into non-collagen protein of the posterior cerebral artery or the mesenteric artery was greater in SHR than WKY. Young SHR were treated with either clonidine or 6-hydroxydopamine (6-OHDA). Administration of clonidine decreased the rate of incorporation of 3H-proline into the non-collagen protein of these arteries concomitantly with a reduction of blood pressure in each rat strain. Administration of 6-OHDA slightly decreased the incorporation of the proline into the non-collagen protein of the SHR posterior cerebral artery, but failed to reduce blood pressure in each rat strain. Ultrastructural pictures of the posterior cerebral arteries of the SHR showed numerous adrenergic ganglion cells. Thus, neural factors, especially in the cerebral arteries, may regulate vascular protein synthesis and may be important for the initiation of hypertension in SHR.
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PMID:Increased non-collagen protein synthesis in the posterior cerebral artery in spontaneously hypertensive rats. 309 82

Angiotensin II (Ang II) produces a positive inotropic effect on the heart; however, its usefulness as an inotropic agent is limited because of its inherent vasoconstrictor action. We therefore designed Ang II analogues that are potent, positive inotropic agents with minimal myotropic properties. Replacement of the proline residue in position 7 with alanine reduced the pressor and vascular contractile response to less than 1% of Ang II. In spite of negligible vascular actions, however, [7-alanine]Ang II produced 50% of the inotropic activity of Ang II in the cat papillary muscle. The results of pharmacological evaluation of various position 7-substituted analogues were as follows: 1) Replacement of proline in position 7 of angiotensin I (Ang I) and Ang II with primary amino acids produced cardiac-specific, positive inotropic properties. 2) The selectivity of positive cardiac inotropic activity of position 7-substituted analogues of Ang II was dependent upon the nature of the amino acid in position 1. Replacement of aspartic acid in position 1 with sarcosine increased vasoconstrictor activity, thereby diminishing cardiac selectivity. However, this change did not affect cardiac selectivity in Ang I analogues. 3) Introduction of any type of steric hindrance in position 7 (e.g., replacement of alanine with N-methyl- or alpha-methylalanine) led to a considerable loss in inotropic activity. In conclusion, contrary to rigid, structural requirements (solution conformation) for the pressor action of Ang II, a less organized structure or a random conformation at the carboxyl terminus appears to favor cardiac-selective contractile response (or positive inotropic response).
Hypertension 1988 Feb
PMID:Angiotensin analogues that selectively augment the force of contraction of the isolated heart. 334 64

A study was made of the vascular protein synthesis in young, genetically hypertensive rats, mainly in their renal arteries. Some of the rats were treated either with 3.5 mg/kg of phenoxybenzamine (POB) or with 4 mg/kg of propranolol twice daily, from 6 to 8 weeks of age. 3H-proline was injected intravenously into each rat before sacrifice to analyse the in vivo incorporation rates of tritiated proline into the vascular collagen and vascular non-collagenous proteins. Evidence has been presented that: (1) the rates of incorporation of 3H-proline into collagen and non-collagenous proteins of the renal arteries in spontaneously hypertensive rats (SHR) and stroke-prone spontaneously hypertensive rats (SHRSP) were greater than those in normotensive Wistar Kyoto rats (WKY); (2) the administration of POB decreased incorporation of 3H-proline into the collagen and non-collagenous proteins of the renal arteries concomitant with a reduction of blood pressure in every rat strain; (3) the administration of propranolol failed to decrease the incorporation of 3H-proline into these connective tissue proteins in the renal arteries and this drug did not reduce blood pressure in every rat strain; (4) the incorporation rates of 3H-proline into these protein fractions in hearts were similar in every rat strain which received any drug treatment. These results indicate that an increased synthesis of collagen and non-collagenous proteins in the renal arteries of young SHR and SHRSP rats participates in the pathogenesis of spontaneous hypertension in the early hypertensive stage.
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PMID:Enhanced protein synthesis in the renal arteries of genetically hypertensive rats: its possible role in causing hypertension. 399 8

Collagen synthesis is increased in the aortas, mesenteric arteries, and to a lesser extent, in the hearts of rats either made hypertensive with desoxycorticosterone acetate-salt or that are spontaneously hypertensive. Several markers of collagen biosynthesis were shown to be increased, including prolyl hydroxylase (EC 1.14.11.2; proline, 2-oxoglutarate dioxygenase), prolyl hydroxylase-related antigen, total collagen content, and the incorporation of [(3)H]proline into total protein and into collagen. The antihypertensive agents chlorothiazide and reserpine, when administered before the onset of hypertension in the rats treated with desoxycorticosterone acetate-salt, prevented or diminished the increase in collagen biosynthesis. When reserpine was given after the onset of hypertension, prolyl hydroxylase activity was decreased concomitant with the decrease in blood pressure. Treatment with reserpine is particularly effective in diminishing arterial prolyl hydroxylase activity.
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PMID:Increased collagen synthesis in blood vessels of hypertensive rats and its reversal by antihypertensive agents. 437 97

Changes in arterial collagen synthesis and the effects of P-1894B, a potent inhibitor of prolyl hydroxylase, were investigated on rat hypertension, induced by deoxycorticosterone acetate (DOCA) and salt. In DOCA-salt hypertensive rats, prolyl hydroxylase activity increased significantly in the abdominal aorta and in the mesenteric artery. Incorporation of 14C-proline into the thoracic aorta, abdominal aorta and mesenteric artery was higher and the hydroxyproline content of the abdominal aorta and mesenteric artery was higher than in the control rats. Treatment with P-1894B significantly inhibited prolyl hydroxylase activity, reduced arterial collagen synthesis, but did not prevent or reverse hypertension.
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PMID:Effects of prolyl hydroxylase inhibition on arterial collagen synthesis and blood pressure in hypertensive rats. 609 59

Rabbit brain endo-oligopeptidase B inactivates angiotensin I (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu) and angiotensin II (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe) by hydrolysis of the Pro7-Phe8 peptide bond. The site of hydrolysis was determined in preparative and analytical experiments in which both products were recovered in a molar ratio of 1:1, and the sum of the products plus unhydrolyzed substrate accounted for the starting material. The enzyme has a Km of 6.3 x 10(-5) M for angiotensin II at pH 8.3 and is activated 30-fold with 4.8 mM dithiothreitol. BPP9a ( less than Gln-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro, SQ 20,881) inhibits the inactivation of angiotensin II with an I50 of 5 x 10(-5) M. BPP5a (less than Gln-Lys-Trp-Ala-Pro, SQ 20,475) is less active and D-3-mercapto-2-methylpropanoyl-L-proline (captopril, SQ 14,225) has essentially no activity. These endo-oligopeptidase B in angiotensin I and II metabolism remains to be established.
Hypertension
PMID:Brain endo-oligopeptidase B: a post-proline cleaving enzyme that inactivates angiotensin I and II. 617 71

The results of this study indicate that both cell proliferation and increased synthesis of extracellular matrix protein contribute to hypertrophy of the rat pulmonary trunk during the early development of hypoxia-induced pulmonary hypertension. As determined by autoradiography after 3H-thymidine injection, pulmonary hypertension results in increased labelling in all cell compartments of the pulmonary trunk wall, the most dramatic response occurring in the adventitia following 3 days' hypoxic exposure. Autoradiography also demonstrated differences in the degree of incorporation of 3H-proline into extracellular protein between hypoxic (3 and 21 days) and control rats. The major focus of 3H-proline incorporation shifted from the adventitia at 3 days to the tunica media at 21 days, although incorporation was significantly higher at 3 compared to 21 days in all wall compartments. The patterns of hyperplasia and matrix protein synthesis in the extrapulmonary arteries of the rat, as reported here, are distinctly different from those seen in many large elastic arteries during development of systemic hypertension. For example, the hyperplastic response of arterial vessels follows a similar temporal sequence in pulmonary and systemic hypertension. However, the adventitia is the region of the pulmonary trunk with highest cell proliferation in pulmonary hypertension while the media is most affected by systemic hypertension. The relevance of the changing patterns of cell proliferation and protein synthesis in the wall of the pulmonary trunk of chronically hypoxic rats to the structural and biochemical properties of this vessel during the early development of pulmonary hypertension is discussed.
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PMID:Autoradiographic analysis of cell proliferation and protein synthesis in the pulmonary trunk of rats during the early development of hypoxia-induced pulmonary hypertension. 623 Jan 23

The renin-angiotensin system was evaluated by inhibition of converting enzyme (CEI) and by testing sensitivity to angiotensin II (AII) in sodium-depleted rats made hypertensive by methylprednisolone (MP), 20 mg/kg im. During a 2-wk period blood pressure rose 38 +/- 4 mmHg (P less than 0.001) in MP and 3 +/- 4 mmHg in controls. After pentobarbital anesthesia, intra-arterial pressure and dose-response curves to AII were determined, before and after SQ14225 (d-3-mercapto-2-methylpropranoyl-l-proline) (1 mg/kg iv). CEI reduced pressure significantly in both MP and controls, although the decrease was smaller in the former (P less than 0.05). Pressor responses to AII were nearly identical in MP and controls and were enhanced to a similar extent by CEI. Ganglionic blockade with pentolinium tartrate, given after CEI, did reduce the pressure in both groups to equal levels. Responses to AII after pentolinium were similar to those obtained after CEI alone. These results indicate that the renin component of glucocorticoid hypertension during sodium deficiency is smaller than that of the normotensive controls. No evidence of glucocorticoid-induced vascular hypersensitivity to AII was detected in this model of experimental hypertension.
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PMID:Effect of converting enzyme inhibition on glucocorticoid hypertension in the rat. 624 27

A synthetic orally active angiotensin I converting enzyme inhibitor Captopril (Squibb), (D-2-methyl-3-mercaptopropanoyl-L-Proline), was administered to three groups of hypertensive animals. The animals were made hypertensive by uninephrectomy, daily injections of 5 ug/100 g body weight d-aldosterone (Sigma) in wheat germ oil and substitution of 0.9% NaCl for the drinking water. Captopril was given to pregnant and nonpregnant animals during the developmental phase of hypertension and to nonpregnant animals with established (4 weeks of treatment) hypertension. The agent attenuated the hypertension in both the pregnant and nonpregnant animals when given while hypertension was developing. Captopril was effective in reducing established aldosterone-NaCl hypertension to normotensive levels.
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PMID:Aldosterone-induced hypertension: effects of a kininase inhibitor. 625 45

A 93,000 molecular weight protein (HBP.93) which binds hemin and protoporphyrin IX with high affinity has been isolated from rabbit serum using affinity chromatography on hemin-conjugated agarose. The amino acid composition of this protein is unique in that the proline and histidine contents are remarkably high (16.6 and 9.9 mol %, respectively). A large increase in the absorbance of the Soret region arises from the heme-protein interaction. The spectrophotometric titration showed that the protein can bind 25-35 mol of hemin/mol of protein. The apparent dissociation constant was estimated to be 1-4 X 10(-7) M for hemin at pH 7.4 and approximately 10(-6) M for protoporphyrin IX at pH 9.2. The similarity of the difference spectrum of heme-HBP.93 complex to that of heme-hemopexin complex suggests that a bisimidazol-type coordination of heme iron is involved in the binding. The extremely high capacity of HBP.93 to bind heme is also demonstrated by a large increase in the sedimentation velocity of the protein upon heme binding. The native heme-protein complex migrates faster than the heme-free protein in a polyacrylamide gel at pH 8.8; the increased mobility appears to be due to the charge on the carboxyl groups of the bound heme. Although the use of a hemin-agarose column has failed to reveal a protein of similar size and heme affinity in the sera of a number of other species, including man, the heme-binding properties and high histidine level of the human alpha 2-histidine-rich glycoprotein raise the possibility that the two proteins are related.
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PMID:A protein with multiple heme-binding sites from rabbit serum. 627 54


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