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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasma renin activity, plasma renin substrate (angiotensinogen), angiotensin I (AI), and plasma angiotensinase activity were measured in 8 women who had first become hypertensive during a mean 3.1 years on various oral contraceptives, and in 5 normotensive women, before and after 1 cycle of pills. All were determined by radioimmunoassay. 8 or more blood pressures were taken by 2 observers and averaged. Plasma renin activity increased from mean 2.12 to 3.52 ng/ml/hr (p greater than .2) in normal women, and from 3.0 to 5.06 in hypertensives (p less than .02). The mean plasma renin substrate values for both groups together rose from 1881 ng/ml to 4245 ng/ml. Angiotensin I rose from .029 ng/ml/hr to .049 in normals, and .027 to .037 in hypertensives. Mean plasma angiotensinase activity values rose from 3.6 to 5.4% degraded per minute in normal women and varied only from 6.5 before and to 5.9 after a pill cycle in hypertensive patients. The authors suggest that development of hypertension during oral contraceptive therapy may be due to abnormal inactivation of angiotensin.
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PMID:Effect of oral contraceptive therapy on the renin-angiotensin system in normotensive and hypertensive women. 434 64

The important role of the renin-angiotensin system (RAS) in the maintenance of high blood pressure in certain forms of hypertension is well established. Inhibition of the RAS has therefore been studied with the aim to develop antihypertensive agents. Pharmacologic interferences with the RAS are possible at all steps of the formation, action and degradation of angiotensin II (ANG II). Renin activity can be inhibited by peptide analogues of angiotensinogen, peptides derived from the amino terminal sequence of pro-renin, inhibitors of acid proteases (pepstatin) and by specific renin antibodies. Inhibitors of the converting enzyme also prevent the formation of ANG II. ANG II receptor blockers (saralasin) prevent the action of the effector peptide of the RAS at the target cells. While some modes of intervention are still theoretical or experimental possibilities, others, e.g. inhibition of converting enzyme, are already used clinically for antihypertensive treatment.
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PMID:Pharmacological interferences with the renin-angiotensin system. 609 63

This paper describes the first case of an angiotensinogen-producing tumor. The tumor obtained from a hypertensive patient was examined for its renin and angiotensinogen contents. Renin activity was undetectable; however, the angiotensinogen level was extremely high compared with the levels in the tissue surrounding the hepatoma. The presence of angiotensinogen immunoreactivity in the tumor cells was demonstrated by immunohistochemical staining with an angiotensinogen anti-serum. The plasma level of angiotensinogen was also markedly elevated. These results strongly suggest that the hepatoma was an angiotensinogen-producing tumor.
Hypertension
PMID:Angiotensinogen-producing hepatocellular carcinoma. 609 44

The renin-angiotensin system is an important regulator of vascular resistance in many patients with hypertension and congestive heart failure. To quantitatively evaluate this contribution requires correlation of markers of the renin-angiotensin system with haemodynamic parameters, notably blood pressure, cardiac output, and calculated systemic vascular resistance. In addition, to determine ventricular loading properties, assessment of cardiac filling pressures is also required. The availability of specific pharmacological inhibitors of the renin-angiotensin system greatly enhances such correlation, as the haemodynamic consequence of blocking the renin-angiotensin system can then more fully identify its contribution. In the last decade, highly specific pharmacological inhibitors have become available to serve such a purpose. Renin inhibitory peptides, and renin-specific antibodies can block the rate-limiting step of the renin-angiotensin cascade: namely, the cleavage of 4 amino acids from the angiotensinogen substrate by renin. However, this method of blockade is still at the early stages of investigation. More readily available are converting enzyme inhibitors which block the formation of angiotensin II, the potent vasoconstrictor which mediates increased systemic vascular resistance, and angiotensin II analogues which compete with endogenous angiotensin II for vascular and adrenal receptors. Although hypertension and chronic congestive heart failure are clinically distinct entities in many respects, their common bond is the fact that both pathological mechanisms are mediated by an increase of systemic vascular resistance. The implications of blocking the resulting vasoconstriction in both entities are therefore quite similar. This review summarises our present knowledge of the contribution of the renin-angiotensin system to the vasoconstriction of hypertension and congestive heart failure, and also summarises the haemodynamic consequences of such inhibition. The implications of the response to these specific pharmacological probes, as well as their limitations, are discussed. Their importance rests not only in their therapeutic application, but also in their contribution as probes for pathophysiological mechanisms of vasoconstriction in cardiovascular disease.
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PMID:Haemodynamic responses to specific renin-angiotensin inhibitors in hypertension and congestive heart failure. A review. 620 42

Tonin is an enzyme of the serine protease family present in different rat tissues which releases angiotensin II (AII) directly from angiotensinogen and the tetradecapeptide renin substrate and from angiotensin I (AI). Tonin potentiates the effect of norepinephrine (NE) in the rat mesenteric artery preparation and in the aortic strips from normal and hypertensive rats. In rabbit aortic and mesenteric artery strips tonin potentiates the effect of NE, almost doubling its response. A similar effect was observed on the KCl and AII-induced contraction. This tonin-induced potentiation is reversible and long-lasting, persisting for 1 to 2 hours after being added into the tissue bath. In 75% of the vascular strips assayed, tonin elicited a contraction with a short latency period and with a maximum tension ranging from a few milligrams to over 1 g. To clarify the mechanisms of tonin effect on vascular smooth muscle, a variety of agents have been used. Neither indomethacin, saralasin, nor alpha- or beta-adrenergic blockers changed the direct contraction or the potentiation induced to NE. Db-cAMP and theophylline blocked the potentiation to the response to NE. A Ca2+-free medium, La3+, and verapamil produced a 75% inhibition of the direct tonin-induced contraction. Papaverine, isoproterenol, and theophylline relaxed the same contraction. Enzymatic inactivation of tonin blocked completely the direct contraction but not the potentiation to NE. These experiments suggest that the vasoactive effect of tonin may be mediated by the release of intracellular-bound calcium, an effect dependent on a proteolytic effect of tonin, and by increasing the cellular permeability to calcium, which is not of a proteolytic effect. It is suggested that tonin remains attached to the vascular strips by mechanisms as yet not clarified.
Hypertension
PMID:Effects of tonin, an angiotensin II-forming enzyme, on vascular smooth muscle in the normal rabbit. 626 53

Many avian species demonstrate atherosclerosis and high blood pressure (BP) that are influenced by age, sex, diet, and environment, but show no arteriosclerosis in small vessels. Thus, we aimed to define neural and humoral control of BP in conscious, 32-wk-old female chickens, Gallus gallus. Mean aortic pressure (determined by chronically implanted catheter) was 137.6 +/- 2.0 mm Hg; heart rate was 295 +/- 4 beats/min. Plasma renin activity (PRA), measured by radioimmunoassay of fowl angiotensin I ([Asp1, Val5, Ser9]AI), and plasma angiotensinogen levels were 3.55 +/- 0.31 ng/ml/hr and 1229 +/- 66 ng/ml respectively. Repeated injection of propranolol (4 to 8 mg/kg/day, i.m.) decreased (p less than 0.01) the BP 19.1 +/- 3.0 mm Hg and heart rate 76 +/- 6 beats/min. Acute infusion of propranolol also markedly reduced BP and heart rate, and increased plasma levels of norepinephrine and epinephrine. SQ 14,225 (20 mg/kg/day) reduced BP (p less than 0.01), but BP returned towards original levels unless a higher dose was given. PRA increased 2- to 6-fold. BP also decreased 31.0 +/- 2.1 mm Hg after reserpine treatment, but not after [Sar1, Ile8]AII. These results suggest that in maintaining BP in fowl the beta-adrenergic function is important, whereas the renin-angiotensin system may not have a primary role.
Hypertension
PMID:Renin-angiotensin and adrenergic mechanisms in control of blood pressure in fowl. 626 58

Angiotensin II-sensitive neurons in the brain of spontaneously hypertensive rats (SHR-sp) and of Wistar Kyoto rats (WKY) treated with the angiotensin-converting enzyme inhibitor Captopril were investigated for possible differences at receptor sites. Furthermore, the concentrations of angiotensinogen and renin were measured in different brain regions of these animals by biochemical assay. The higher receptor sensitivity of septal neurons to angiotensin II which existed in SHR-sp as compared to WKY was diminished by Captopril. Angiotensinogen concentrations were lower in the anterior hypothalamus but not in the septum of SHR-sp as compared to WKY. Captopril increased the level in both strains. Renin concentrations did not differ in SHR-sp and WKY. Chronic treatment with Captopril induced an increase of about 20% in septum and hypothalamic regions of SHR-sp and WKY rats. Whether these changes are causally linked to the hypertension in SHR-sp remains to be investigated.
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PMID:Angiotensin-converting enzyme blockade by Captopril changes angiotensin II receptors and angiotensinogen concentrations in the brain of SHR-sp and WKY rats. 629 70

The brain renin-angiotensin system (RAS) has been suggested as contributing to the pathogenesis of spontaneous hypertension in rats. Brain angiotensinogen- and angiotensin II (AII)-sensitive neurons were therefore investigated in stroke-prone spontaneously hypertensive rats (SHR-sp) and in Wistar-Kyoto (WKY) rats with and without treatment by captopril (CAP). Angiotensinogen was decreased in the anterior hypothalamus but increased in the cortex, the hippocampus, and cerebellum of SHR-sp. There were no differences between SHR-sp and WKY rats concerning the angiotensinogen content of posterior hypothalamus, brain stem, and septum. The sensitivity of the septal neurons to microiontophoretically applied AII was elevated, however, in SHR-sp as compared to WKY rats with regard to threshold and maximal response for AII-evoked neuronal discharges. The excitation characteristics did not change with the age of animals in both WKY rats and SHR-sp. The treatment of SHR-sp with CAP (50 mg/kg/day per os) starting in weanlings kept animals normotensive and reduced the high sensitivity of septal neurons to AII. Simultaneously angiotensinogen content was increased in the anterior hypothalamus and suppressed in the hippocampus. The same treatment of WKY rats reduced blood pressure somewhat and increased the angiotensinogen content in the anterior hypothalamus without affecting the neuronal sensitivity to AII. Thus, malfunction of the brain RAS may participate in the hypertension of SHR-sp, since converting enzyme blockade with CAP inhibited the blood pressure rise, augmented the angiotensinogen content of the anterior hypothalamus, and decreased the sensitivity of AII receptors in the brains of these rats.
Hypertension
PMID:Influence of captopril treatment on angiotensin II receptors and angiotensinogen in the brain of spontaneously hypertensive rats. 631 52

The proteolytic enzyme renin (EC3.4.99.19) cleaves the protein substrate angiotensinogen to yield angiotensin I, the decapeptide substrate transformed by converting enzyme into the pressor substance angiotensin II. Although the contribution of this pathway to the maintenance of normal blood pressure is unclear, it seems to be a major factor in various hypertensive states. Important progress in the control of hypertension has been achieved by development of the potent inhibitors SQ-14,225 (captopril) and MK-421 (enalapril maleate), which block the generation of angiotensin II by the inhibition of angiotensin converting enzyme. An attractive alternative to the inhibition of converting enzyme would be the blockade of the preceding step in the cascade, the renin reaction. We report here new highly potent (IC50 = 10(-9)-10(-8) M) competitive inhibitors of renin in which statine, (3S,4S)-4-amino-3-hydroxy-6-methylheptanoic acid, is incorporated into analogues of the pig renin substrate (Fig. 1).
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PMID:Novel renin inhibitors containing the amino acid statine. 634 56

Renin is an aspartyl proteinase that catalyses the first, and rate-limiting, step in the conversion of angiotensinogen to the hormone angiotensin II. The catalysis is highly specific, and plays an important physiological part in the regulation of blood pressure. For this reason inhibitors of renin are of potential value in the treatment of certain forms of hypertension. Although progress has been made in the design of inhibitors for clinical use by modification of angiotensinogen sequences, and as pepstatin analogues or with reduced peptide bonds, we have now provided the basis for a more rational approach by the use of interactive computer graphics techniques to build a three-dimensional model of renin. The model is based on the three-dimensional structure of endothia pepsin and the primary structure of mouse renin, which is very similar to that of the human enzyme. We show that renin may have a three-dimensional structure similar to that of other aspartyl proteinases.
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PMID:Three-dimensional structure, specificity and catalytic mechanism of renin. 634 9


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