Mechanisms of the nitroglycerine‐induced vasodilation in vascular smooth muscles of the rabbit and pig.

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Abstract
The effects of nitroglycerin (NG) on the mechanical responses of small pieces of intact and skinned smooth muscles of the mesenteric artery were investigated, as were the Ca fluxes of isolated smooth muscle cells of the coronary artery. NG (10-6-10-5 M) inhibited both phasic and tonic components of the K-induced contraction; however, the tonic component was more sensitive to NG. The minimum concentration of NG required to decrease significantly the tonic response evoked by 39 mM external K was 10-8 M. NG (10-5 M) reduced the number of oscillatory contractions evoked by 10-5 M noradrenaline (NAd) [norepinephrine]. After complete removal of stored Ca, the addition of Ca did not produce contraction in polarized muscle (5.9 mM external K), yet depolarized muscles (128 mM external K) did contract. Addition of NG (10-5 M) with Ca produced no change in the resting tone in polarized muscles but inhibited the contraction in depolarized muscles. After application of NG (10-5 M), caffeine or NAd consistently produced smaller contraction in both polarized and depolarized muscles in Ca-free solution. NG (10-5 M) inhibited the Na-free contraction evoked by prolonged treatment with Na-free solution. Contractions evoked by repetitive applications of 10-5 M NAd or 10 mM caffeine persisted longer in Na-free, Ca-free (EGTA [ethylene glycol bis(.beta.-aminoethyl ether) N,N''-tetraacetic acid] solution than those observed in Ca-free Krebs solution, but when NG was added to the Na-free, Ca-free (EGTA) solution, the contractions ceased more rapidly than in the absence of NG. In chemically skinned muscles, 10-5 M NG had no effect on the pCa-tension relationship. The absolute amplitude of Ca-induced contraction was also not affected by 10-5 M NG. In these muscles, when the amount of stored Ca was estimated from the amplitude of the caffeine-induced contraction, Ca accumulation into and release from store sites were unaffected by 10-5 M NG. The effects of 10-5 M NG on the accumulation and efflux of 45Ca in isolated cell suspensions prepared from the porcine coronary artery were investigated. The amount of 45Ca taken up by cells after 1-30 min incubation in 45Ca-containing solution, and the 45Ca efflux in Ca-free (EGTA) solution, were not affected by 10-5 M NG. In the presence of 3 .times. 10-6 M acetylcholine (ACh), the efflux of 45 Ca into Ca-free (EGTA) solution was accelerated and with the addition of 10-5 M NG plus 3 .times. 10-6 M ACh, this efflux was even further enhanced. Relaxation of vascular smooth muscle tissues by application of NG is evidently to some extent related to the inhibition of Ca influx, but is mainly due to acceleration of extrusion of Ca after it is mobilized from stores by appropriate stimulatory agents.