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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Renin angiotensin system parameters and blood pressure (B.P.) were followed monthly in patients with essential hypertension on metolazone, 5 mg daily for three months and with added propranolol, 40 to 160 mg, for the subsequent three months. On metolazone alone at three months, sitting B.P. declined from 166/108 +/- 14/11 mm Hg to 145/98 +/- 14/9 mm Hg (P less than 0.005). Plasma renin activity (PRA) increased from 3.9 +/- ng/ml/hr to 10.4 +/- 8.6 ng/ml/hr (P less than 0.005); plasma angiotensinogen did not change. Venous blood angiotensin I and II levels (pg/ml) rose initially but returned toward control values. A significant decline in plasma renin substrate reactivity (PRSr) in index occurred. Propranolol addition caused further lowering of only systolic B.P. and predominantly in the standing position, more marked at one month (40 mg) than at three months (160 mg). No significant further changes were observed in any of the measured parameters of renin angiotensin system, except for a rise in PRSr index concomitant with B.P. elevation at three months. Metolazone-induced changes in B.P. showed significant correlations at three months with changes in PRSr index. It is concluded that during chronic metolazone administration, the overall activity of the renin angiotensin system was diminished or unchanged. Propranolol did not inhibit metolazone stimulated PRA but did cause further decline in B.P. in the first two months, unrelated to renin angiotensin system.
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PMID:Antihypertensive and renin angiotensin effects of metolazone with and without propranolol. 84 95

Essential hypertension is a common human disease believed to result from the interplay of multiple genetic and environmental determinants. In genetic studies of two large panels of hypertensive sibships from widely separated geographical areas, we obtained evidence of genetic linkage between the angiotensinogen gene (AGT) and hypertension, demonstrated association of AGT molecular variants with the disease, and found significant differences in plasma concentrations of angiotensinogen among hypertensive subjects with different AGT genotypes. The corroboration and replication afforded by these results support the interpretation that molecular variants of AGT constitute inherited predispositions to essential hypertension in humans.
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PMID:Molecular basis of human hypertension: role of angiotensinogen. 139 29

Renin plays a major role in the control of blood pressure and water and electrolyte metabolism and it is clear that blocking of this system is particularly effective in the treatment of essential hypertension and heart failure. A large number of converting enzyme inhibitors have been synthesized. Converting enzyme inhibitors are remarkably active in heart failure and they reduce microalbuminuria and possibly maintain glomerular function. Blocking of the renin-angiotensin system by converting enzyme inhibitors is not accompanied by hypotension or reflex stimulation of the sympathetic nervous system. Converting enzyme inhibitors represent a major therapeutic advance in the field of cardiovascular and renal disease but the long-term effects of decreased angiotensin II levels are unknown. There are other ways to inhibit the renin-angiotensin system. The recent discovery of orally-active non-peptide angiotensin II antagonists opens a range of fascinating prospects. Another approach consists in inhibiting the reaction of renin on angiotensinogen, which is remarkably selective. Although it is too early to know whether these new approaches will be less active, more active or as active as current converting enzyme inhibitors, they may constitute a progress in relation to currently available treatments.
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PMID:New therapeutic prospects of renin-angiotensin system inhibition. 269 Nov 25

Although renin was identified as playing a part in cardiovascular homeostasis by the experiments of Goldblatt in the 1930s, neither its physiological role in organs other than the kidney nor its contribution to the genesis of essential hypertension have been defined. It is difficult to interpret studies with converting enzyme inhibitors because of their multiple pharmacological effects. Specific inhibitors of renin appropriate for clinical investigation would help to resolve many questions. Four classes of compounds have been shown to be renin inhibitors of high potency: specific antibody, general peptide inhibitors of acid proteases, analogues of angiotensinogens and peptides that are related to the amino-terminal sequence of prorenin. Of these, it is likely that angiotensinogen analogues will be the first applied in human studies. The minimal substrate for renin has the sequence: His-Pro-Phe-His-Leu-Val-Tyr. Variants of this sequence have yielded competitive inhibitors. Remarkably active compounds have recently been synthesized by reducing the peptide bond that is cleaved by renin, or by incorporating the amino acid statine, found in pepstatin. These compounds have been shown to be effective in dogs, rats and monkeys and, most recently, preliminary studies have reported their efficacy in man. Recent studies with one of these inhibitors, RIP, raise questions concerning both its specificity and site of action.
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PMID:Will renin inhibitors influence decision-making in antihypertensive therapy? 300 3

We measured components of the cerebrospinal fluid renin-angiotensin system from patients with essential hypertension under different dietary sodium intakes. The cerebrospinal fluid concentration of angiotensin II (Ang II) from the patients on a normal-sodium diet was 1.36 +/- 0.41 fmol/ml (n = 5). Neither the inactive nor the active form of renin was detected by the enzymatic activity or by the immunoreactivity, whereas angiotensinogen was detected (38.6 +/- 3.1 pmol/ml, n = 5). The Ang II level remained unchanged even after incubation of the cerebrospinal fluid at 37 degrees C for 3 h. Further, when authentic Ang II was added to the cerebrospinal fluid followed by incubation for 3 h at 37 degrees C, more than 90% of the added Ang II remained unchanged. Thus, the cerebrospinal fluid Ang II level may be reflected by the activity of the brain Ang II-forming system, as it was not affected by the cerebrospinal fluid constituents. The circulating renin-angiotensin system was stimulated by sodium depletion, and the cerebrospinal fluid concentration of Ang II also increased significantly. Sodium depletion may stimulate the brain Ang-II forming system, as it does the circulating renin-angiotensin system.
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PMID:Cerebrospinal fluid angiotensin II in patients with essential hypertension. 307 91

Components of the renin-angiotensin system (plasma renin activity, total and inactive renin, angiotensinogen and angiotensin II) were examined in 90 patients with labile and stable essential hypertension before and after functional and pharmacologic tests. New data have been obtained on intrasystemic regulatory mechanisms of the pressor renin-angiotensin systems. Different patterns of plasma active and inactive renin variations in response to salt loading are demonstrated in patients with different "renin" variants of essential hypertension. Angiotensin II is shown to have a stimulating effect on angiotensinogen synthesis.
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PMID:[Correlation of the total activity of blood plasma renin with levels of active and inactive renin, angiotensinogen and angiotensin II under different functional loads in patients with hypertension]. 328 15

Although renin was identified as playing a role in cardiovascular homeostasis by the experiments of Goldblatt in the 1930's, neither its physiologic role in organs other than the kidney nor its contribution to the genesis of essential hypertension has been defined as yet. It is difficult to interpret studies with converting enzyme inhibitors because of their multiple pharmacologic effects. Specific inhibitors of renin appropriate for clinical investigation would help resolve many questions. Four classes of compounds have been demonstrated to be renin inhibitors of high potency: specific antibody, general peptide inhibitors of acid proteases, analogs of angiotensinogens, and peptides that are related to the amino-terminal sequence of prorenin. Of these, it is likely that angiotensinogen analogs will be the first applied in human studies. The minimal substrate for renin has the sequence: His-Pro-Phe-His-Leu-Leu-Val-Tyr. Variants of this sequence have yielded competitive inhibitors. Recently, remarkably active compounds have been synthesized by reducing the peptide bond that is cleaved by renin, or by incorporating the amino acid statine, found in pepstatin. These compounds have been shown now to be effective in dogs, rats, and monkeys, and most recently, preliminary studies have reported their efficacy in humans. Recent studies with one of these inhibitors, RIP, raise questions concerning both its specificity and site of action.
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PMID:Defining the physiologic and pathophysiologic roles of renin: the role of specific inhibitors. 388 1

Among 25 patients with benign, essential hypertension, and an equal number with other benign forms of hypertension, without serious cardiac, renal, or cerebrovascular impairment, 41 cases failed to reduce aldosterone excretion rates into the normal range (less than 5 mug/day) on a daily intake of 300 mEq of sodium. The hypertensive patients excreted slightly less than the normal fraction of labeled aldosterone as acid-hydrolyzable conjugate. Secretion rates were significantly higher in the hypertensive patients than in normotensive controls taking the high-sodium intake. On a 10 mEq sodium intake, the increase in excretion and secretion rates of aldosterone in the hypertensive patients could be correlated with plasma renin activity (PRA). The patients with the least increase in PRA had subnormal increase in aldosterone secretion and excretion, while unusually large rises in aldosterone secretion accompanied high PRA, especially in the cases with increased plasma angiotensinogen induced by oral contraceptives. The persistence of inappropriately high aldosterone secretion in most hypertensive patients during sodium loading could be related to a higher PRA than that found in normotensive controls under comparable conditions. In other hypertensives, whose PRA was unresponsive to sodium depletion, there was no significant correlation between PRA and aldosterone output, and no known stimulus to aldosterone production was detected. Five obvious cases of hyperaldosteronism were found among the 16 low-renin patients. The cause of the nonsuppressible aldosterone production in the other low-renin cases remains to be determined.
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PMID:Abnormally sustained aldosterone secretion during salt loading in patients with various forms of benign hypertension; relation to plasma renin activity. 431 84

The enzyme renin splits a single peptide bond in the plasma glycoprotein angiotensinogen liberating the biologically inactive decapeptide angiotensin I (ANG I). A second enzyme, angiotensin converting enzyme (CE), releases the strong vasoconstricting octapeptide ANG II via degradation of a C-terminal dipeptide. The effect of this compound on blood pressure can be attenuated by interference with the enzyme-controlled peptide cascade of the renin-angiotensin system (RAS). This is accomplished by inhibition of renin and CE, respectively. Orally active CE inhibitors are valuable drugs in the treatment of renal and essential hypertension and of heart failure. Strong inhibitors of renin have also been synthesized, however, peptide moieties which have still to be present in these compounds impede oral absorption. Finally, antagonistic analogues of ANG II are able to block its effect on the receptor level. Their application is limited by the still existing partial agonistic activity.
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PMID:Chemistry of the inhibitors of the renin-angiotensin system. 609 62

The precise contribution of the renin-angiotensin system to the genesis of essential hypertension is difficult to discern from clinical studies with converting enzyme inhibitors because of their multiple pharmacological effects. Specific inhibitors of renin, appropriate for clinical investigation, would help to resolve this question. Four classes of compounds have been demonstrated to be renin inhibitors of high potency: specific antibodies, general peptide inhibitors of acid proteases, analogues of angiotensinogens, and peptides related to the amino-terminal sequence of prorenin. Of these, it is likely that angiotensinogen analogues will be the first to be applied in human studies. The minimal substrate for renin has the sequence: His-Pro-Phe-His-Leu-Leu-Val-Tyr. Variants of this sequence have yielded competitive inhibitors. Recently, remarkably active compounds have been synthesized by reducing the peptide bond cleaved by renin or by incorporating the amino acid statine, found in pepstatin. These compounds have now been shown to be effective in dogs, rats and monkeys, and, according to recent preliminary studies, in man.
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PMID:The first Sir George Pickering memorial lecture. Which inhibitors will give us true insight into what renin really does? 609 85


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