Scytonema hofmanni, a filamentous freshwater cyanobacterium (blue-green alga), produces secondary metabolites which inhibit the growth of other cyanobacteria and green algae. A rapid, qualitative assay for this inhibition has been developed with Synechococcus as the test organism. This assay procedure has led to the isolation and characterization of an antibiotic (named cyanobacterin) from Scytonema. The antibiotic has a molecular weight of 430 and an empirical formula of C23H23O6Cl and contains a gamma-lactone and a chlorinated aromatic nucleus. It inhibits the growth of various algae but has limited effect on nonphotosynthetic bacteria or protozoans and thus may have potential use as a specific algicide.

SUMMARY Inhibition of renin was induced in conscious marmosets with CGP 29 287, Z-Arg-ArgPro-Phe-His-Sta-Ile-Hls-Lys (Boc)-OMe, a renin inhibitor with a prolonged duration of action. In vitro, CGP 29 287 is a potent inhibitor of primate plasma renin (inhibitory concentration, 50%: human = 1 x 10"'M; marmoset = 5 x 10"'M) and less potent against dog (2 x 10~7M)orrat(3 x 10~5 M) plasma renin. CGP 29 287 is a weak inhibitor of other aspartic proteases such as porcine pepsin or bovine cathepsin D (inhibitory concentration, 50% = 4 x 10~5 M). In furosemide-treated marmosets, CGP 29 287 lowered blood pressure and inhibited plasma renin activity during intravenous infusion and after intravenous bolus injection. The duration of action after intravenous injection was dose dependent and ranged from 1 hour after 0.1 mg/kg to more than 3 hours after 10 mg/kg. High doses of CGP 29 287 (100 mg/kg) were active after oral administration. In all experiments a close relation between inhibition of plasma renin activity and reduction of blood pressure was found. A maximum hypotensive response to CGP 29 287 was associated with complete inhibition of plasma renin activity, and the recovery of blood pressure was accompanied by recovery of plasma renin activity. The hypotensive effects of CGP 29 287 were smaller in untreated than in furosemide-treated marmosets. CGP 29 287 had no influence on blood pressure in marmosets after bilateral nephrectomy or after pretreatment with a converting enzyme inhibitor. CGP 29 287 did not affect the pressor responses to exogenous angiotensin I or angiotensin II. These results indicate that CGP 29 287 is a potent and specific inhibitor of primate renin. In furosemide-treated marmosets CGP 29 287 induced a long-lasting reduction in blood pressure that appears to be entirely due to inhibition of renin. (Hypertension 7: 797-803, 1985) KEY WORDS • renin activity converting enzyme inhibitor furosemide • cathepsin D • pepsin • statine T HE renin-angiotensin system (RAS) plays an important role in blood pressure regulation. This finding has led to considerable interest in compounds that inhibit renin, the enzyme that catalyzes the first step in the formation of the biologically active peptide angiotensin II (ANG II).1 -2 One of the first described inhibitors of renin was pepstatin, a peptide of fungal origin.3 The poor solubility, low potency, and lack of specificity of pepstatin restricted its experimental application in vivo. Subsequently, analogues of the amino acid sequence around the cleavage site of angiotensinogen were shown to inhibit renin. However, these compounds were of limited usefulness for studies in vivo because of their low potency and short biological half-life. Recently, more potent ana-

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The effects on blood pressure of an antiserum against pure human kidney renin were studied in conscious and anesthetized (pentobarbital, 24 mg X kg-1 i.p.) small new world monkeys (common marmosets). The antiserum inhibited the enzymatic activity of renin by 50% in a dilution of 1:45,000 in marmoset and 1:50,000 in human plasma. The antiserum (0.2 ml i.v.) decreased blood pressure in conscious marmosets on normal sodium intake by 15 +/- 5 (SD) mmHg and after salt depletion by 31 +/- 13 mmHg. A converting enzyme inhibitor (teprotide, 2 mg X kg-1 i.v.) induced a comparable fall in blood pressure: -16 +/- 10 and -30 +/- 10 mmHg, respectively. Similar effects were observed on blood pressure of anesthetized marmosets. The correlation between pretreatment plasma renin concentration and the maximum fall in blood pressure was significant and identical for the experiments with antiserum and teprotide. These results demonstrate that antisera against human renin can be used for the specific blockade of the renin-angiotensin system in primates. In normotensive marmosets the renin-angiotensin system participates in the maintenance of blood pressure, to a degree depending on the state of sodium balance.

Ten species of freshwater blue-green algae exhibit an adenosylcobalamin-dependent ribonucleotide reductase, thuse explaining the requirement for cobalt by these organisms. The evidence suggests a phylogenetic affinity between the cyanophytes and bacteria, such as Clostridium and Rhizobium, and the euglenoid flagellates, which also use the cofactor-dependent reductase. In contrast, the ribonucleotide reductase reaction in the few green algae surveyed shows no dependence on cobalamins.