Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:Defining the physiologic and pathophysiologic roles of renin: the role of specific inhibitors. 388 1