1 Flosequinan (BTS 49 465, 7-fluoro-1-methyl-3-methylsulphinyl-4-quinolone) a novel arteriovenous dilator agent was orally effective in conscious renal hypertensive dogs and normotensive cats. The hypotensive potency of flosequinan was approximately ten times less than that of hydralazine in renal hypertensive dogs, 10mgkg-1 and 20mgkg-1 flosequinan causing similar falls in mean blood pressure to mg kg-I and 3 mg kg-1 hydralazine respectively. In normotensive cats, 5 mgkg 1 flosequinan caused similar falls to 0.5 and 1.Omgkg 1 hydralazine. The onset of hypotensive effect after flosequinan appeared to be slightly slower than after hydralazine in the dog and slightly faster than hydralazine in the cat. 2 The degree of tachycardia and increase in plasma renin activity (PRA) for equivalent falls in mean blood pressure in both species was significantly less for flosequinan than for hydralazine (P < 0.05). 3 In normotensive dogs, flosequinan, 10 and 2Omgkg-1 orally, caused a small but non-significant increase in sodium and chloride excretion and had little effect on urine volume whereas hydralazine, 1 and 3 mg kg1-orally, caused a marked retention of sodium and chloride ions and a reduction in urine volume (P < 0.01). 4 Neither flosequinan, 10mgkg-1 orally, nor hydralazine 1mgkg-1 orally, affected either glomerular filtration rate measured as creatinine clearance or effective renal plasma flow measured as p-aminohippuric acid clearance in normotensive dogs. 5 The lesser degree of tachycardia and increase in plasma renin activity together with a lack of sodium retaining activity associated with flosequinan suggest that this agent may have potential advantages over existing therapy as an antihypertensive in man.

1. Angiotensin I, II and hog renin, infused into the lateral cerebral ventricles (I.C.V.) of water replete cats, each induced water drinking behaviour. 2. Intravenous infusion of high doses of angiotensin I or II also elicited a drinking response. The dipsogenic effect of I.V. renin was not marked. 3. Drinking in response to I.C.V. angiotensin II was abolished after autonomic ganglion blockade with I.V. hexamethonium or pempidine and was significantly reduced after I.V. atropine methonitrate. 4. The dipsogenic response to I.C.V. angiotensin II was unaffected by either peripheral adrenergic neurone blockade with I.V. bethanidine, alpha‐adrenoceptor blockade with phentolamine or beta‐adrenoceptor blockade with sotalol. 5. Atropine, atropine methonitrate, hexamethonium and pempidine given I.C.V did not inhibit the diposgenic response to I.C.V. angiotensin II. 6. Bethanidine I.C.V. produced a dose related reduction in the dipsogenic response to I.C.V. angiotensin II. 7. The alpha‐adrenoceptor blocking agents tolazoline and phenoxybenzamine given I.C.V did not affect angiotensin induced drinking but the response was regularly inhibited by phentolamine I.C.V. 8. The beta‐adrenoceptor blocking agents propranolol and practolol given I.C.V. each inhibited angiotensin induced drinking. The L‐isomer of propranolol was a more effective blocker than the D‐isomer. 9. Isoprenaline given I.C.V induced drinking in ten of sixteen cats. Subcutaneous administration of isoprenaline also elicited drinking but the onset of the response was delayed and the amount consumed slightly less than after I.C.V infusion.

S U M M A R Y1. Intracerebroventricular (icv) administration of the renin inhibitor pepstatin inhibited the dipsogenic response to icv renin but did not affect drinking induced by icv angiotensin I and 11.2. Intracerebroventricular administration of an angiotensin converting enzyme inhibitor, SQ 20881, reduced the dipsogenic effect of icv renin and angiotensin I but did not affect angiotensin I1 induced drinking.3. Intracerebroventricular administration of SQ 20881 reduced the dipsogenic effect of intravenous angiotensin I but did not reduce drinking elicited by intravenous angiotensin 11. 4. Intracerebroventricular administration of Sarl-Alas-angiotensin 11, a competitive antagonist of angiotensin 11, inhibited drinking elicited by icv renin, angiotensin I and angiotensin 11. The dipsogenic response to intravenous infusion of both angiotensins I and I1 was reduced after central administration of this antagonist.5. Four analogue antagonists of angiotensin I1 given icv reversibly inhibited the dipsogenic response to icv angiotensin 11. These analogues themselves possessed weak dipsogenic effects.6. Renin-angiotensin induced drinking in the cat is mediated by the action of angiotensin I1 on receptors in the central nervous system.

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I Female mice of the Hough/Porton and Tuck/TO strains were found to be more sensitive than male mice to the diuretic effects of oral and intravenous doses of ethacrynic acid. 2 The sensitivity of Hough/Porton male mice to ethacrynic acid was increased after pretreatment with stilboestrol and the sensitivity of female Hough/Porton mice decreased after pretreatment with testosterone.3 There were no significant sex differences in the diuretic response to frusemide, acetazolamide, aminophylline, bendrofluazide, and Su 15049A although a small, but significant, increase in the sensitivity of male Tuck/TO mice to triamterene was noted. 4 The sex difference in diuretic response to ethacrynic acid may be related to an effect of sex hormone balance on its metabolism or on the sensitivity of its renal receptor.