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. 1994 Jun;112(2):533–540. doi: 10.1111/j.1476-5381.1994.tb13106.x

Nitrovasodilator-induced relaxation and tolerance development in porcine vena cordis magna: dependence on intact endothelium.

G Kojda 1, J K Beck 1, W Meyer 1, E Noack 1
PMCID: PMC1910372  PMID: 7521258

Abstract

1. Isolated segments of porcine vena cordis magna exhibited a reproducible contractile activity upon application of prostaglandin F2 alpha (PGF2 alpha) or KCl, that was independent of the presence of intact endothelium. Substance P (3 nM) elicited strictly endothelium-dependent relaxations amounting to 46.1 +/- 1.4% (n = 206) of contractions induced by 10 microM PGF2 alpha. 2. S-nitroso-N-acetyl-D,L-penicillamine (SNAP), a compound that spontaneously liberates nitric oxide, concentration-dependently relaxed PGF2 alpha-precontracted (50 microM) venous segments. Tolerance induction (incubation with 100 microM SNAP for 30 min) within the same segments resulted in a 3 fold attenuation of this effect, which was not further reduced after additional preincubation with glyceryl trinitrate (GTN). Removal of endothelium or the presence of N omega-nitro-L-arginine methylester (L-NAME) significantly improved the potency of SNAP before and after tolerance induction. 3. Concentration-dependent relaxations induced by GTN in non-tolerant veins were similar in the presence and absence of endothelium but much more reduced in tolerant endothelium-denuded (75 fold) compared to intact (20 fold) segments. In contrast, the presence of L-NAME significantly improved GTN-activity solely in non-tolerant veins, which, therefore, also resulted in a more pronounced attenuation of activity due to tolerance induction (100 fold). Preincubation of intact veins with SNAP also reduced GTN-activity but to a lesser extent (10 fold). 4. The more delayed but much longer, and compared to GTN somewhat weaker, acting new nitrovasodilator N-(3-nitrato-pivaloyl)-1-cysteineethylester (SPM 3672) was more potent in denuded than intact non-tolerant venous segments.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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