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Several letters to the editor are presented in response to the article "A British View of the U.S. Policy" in the October 12, 1953 issue.

1,4,5,6,7,8-hexahydro-2-methyl-5-oxo-4-(pentafluorophenyl) -1,7 - naphthyridine - 3 - carboxylic acid methyl ester hydrochlorides with either a 3-phenoxy-2-hydroxypropyl (Wy-46,300) or 2-hydroxy-4-phenylbutyl (Wy-46,531) substituent at the 7 position are structurally novel vascular relaxant compounds which lower blood pressure by ~35 mm Hg at 25 mg/kg p.o. in spontaneously hypertensive rats (SHR) or perinephritic hypertensive beagles. In contrast to standard Ca2blockers, both agents also directly inhibit myosin phosphorylation and actin-myosin interactions in Triton-purified arterial actomyosin. The potency of Wy-46,300 (IC50= 28 µM) in this system is similar to the calmodulin antagonist W-7, whereas Wy-46,531 (IC5= 18 µ M) is more potent. Inhibition of both parameters is attenuated in the presence of maximal Ca2-calmodulin, consistent with calmodulin antagonism as the mechanism for myosin phosphorylation inhibition. In intact smooth muscle, these agents inhibit K-depolarized contractions of rabbit aortic strips in a biphasic manner (0.1–10 µ M, 30–40 inhibition; 10 µ M/-100 µ M, 90 inhibition). In contrast to comparable inhibition of force by standard Ca2blockers, this latter phase of inhibition is not reversible with the Ca2agonist Bay K 8644. Moreover, significantly greater inhibition of receptor-mediated contractions (norepinephrine, angiotensin II, histamine) than that observed with nifedipine is apparent with Wy-46,300. In paced rabbit atria, both Wy-46,300 and Wy-46,531 are 10–100 times less potent as negative inotropic agents (IC25= 3–5 µ M)when compared with standard Ca2blockers. These results suggest that Wy-46,300 and Wy-46,531 are vascular relaxants which appear to act through combined inhibition of Ca2entry and direct inhibition of Ca2calmodulin-dependent activation of myosin phosphorylation.

Arylalkylsulfonamides, identified as Wy-46,622 and Wy-47,324, combine pharmacological properties of the Ca2entry blocker verapamil and the calmodulin antagonist W-7. These agents directly inhibit arterial actin-myosin interactions via inhibition of myosin light chain (MLC) phosphorylation in actomyosin. Potencies of both Wy-46,622 (IC50= 26 μM) and Wy-47,324 (IC50= 18 μM) are greater than W-7 (IC50= 35 μM); verapamil is inactive at 100 μM. Both Wy-46,622 and Wy-47,324 are less potent than verapamil, but more potent than W-7, at inhibiting K-depolarized force development in paced rabbit atria. At higher concentrations (30 μM) which inhibit MLC phosphorylation, Wy-46,622 and Wy-47,324 are either equal to or more efficacious than verapamil in inhibiting receptor-mediated contractions in intact porcine coronary (histamine. serotonin, prostaglandin F2a, carbocyclic thromboxane A2) or guinea pig aortic (leukotriene C4) smooth muscle. Both Wy-47,324 (IC50= 16 μM) and Wy-46,622 (IC50= 23 μM) are inhibitors of the second phase of epinephrine-induced human platelet aggregation; Wy-47,324 is more potent than verapamil or W-7 (IC50for each = 29 μM). These results suggest that these agents possess combined Ca2entry blocker/MLC phosphorylation inhibitory mechanisms. Furthermore, they are more vascular specific than verapamil, and are effective inhibitors of intra-cellular Ca2-mediated events in vascular smooth muscle and platelets.

Reports on the prototype lighting fixtures installed for field testing at the Chicago Housing Authority in Chicago, Illinois. Problem posed by common-area lighting at the public housing; Description of the prototype and field testing; Details on the monitoring and benefits of the lighting fixtures.