Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Orthostatic cardiovascular reflexes were evaluated in conscious cynomolgus monkeys during interruption of the renin-angiotensin system with the renin inhibitor: RIP (Pro-His-Pro-Phe-His-Phe-Phe-Val-Tyr-Lys-OH). RIP was synthesized via solid phase techniques and purified to homogeneity. In vitro studies indicated that it exhibited classical competitive inhibition of renin with a KI of 2.3 microM. In vivo, RIP at 2 mg/kg per min inhibited renin and angiotensin I pressor responses indicating that it was not a specific renin inhibitor at this dose. However, in spite of the nonspecificity, RIP did not affect the supine blood pressure of sodium-replete monkeys, but did evoke hypotension in supine sodium depleted monkeys. RIP did not elicit significant orthostatic hypotension in either sodium-replete or sodium depleted monkeys. The cardiovascular effects of RIP described in this study appear to be due to inhibition of the renin-angiotensin system.
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PMID:Cardiovascular effects of a renin inhibitor in relation to posture in nonhuman primates. 298 82

Seven active tetrapeptide amides characterized by a C-terminal phenylalanyl aminoadamantane (PheNHAd) sequence, were identified by selective testing for human renin inhibitory activity among compounds with adjacent hydrophobic groups and molecular size equivalent to 3-5 amino acid residues. The new inhibitors were compared with known renin inhibitors (RIP, pepstatin, H-77) and opioid analgesic agents (Met-enkephalin, morphine), with the following results: The new inhibitors were active against human renin (IC50 approximately 10-5M), but inactive against rat renin and pepsin. Although active in opiate receptor binding studies (IC50 approximately 10(-7)M), they were, with few exceptions, inactive in the mouse writhing and hot plate tests for analgesia. SAR studies suggested a separation of the renin inhibitory from the analgesic activity of enkephalin analogs. Preliminary experiments with sodium-depleted rhesus monkeys indicated hypotensive activity for three of the new inhibitors at 3 mg/kg i.v., and RIP at 1 mg/kg. The recently reported clinical hypotensive properties of RIP (Zusman et al., Trans. Assoc. Am. Physicians 96:365, 1983) along with the present comparative studies suggest that the new inhibitors may lead to clinically useful agents.
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PMID:New class of inhibitors specific for human renin. 300 Jun 56

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

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