Background: Despite the overwhelming evidence linking smoking and nicotine intake with vascular function impairments, the mechanisms involved and the possible ameliorative effect of black seed (Nigella sativa (NS)) oil administration are not clearly understood. This study sought to determine the involvement of nitric oxide synthase and voltage-sensitive potassium channels in the modulation of vascular reactivity in cigarette or nicotine-exposed rats treated with NS oil.
 Methods: Thirty male Sprague-Dawley rats were divided into 6 groups comprising vehicle control (Control), NS oil only (NS), Smoke only (SMK), Smoke + NS oil (SMKNS), Nicotine only (NCT) and Nicotine + NS oil (NCTNS). Animals were either passively exposed to cigarette smoke or nicotine vapour for 12 weeks, however, NS oil treatment commenced from 9th-12th week orally. At the end of the 12-week experimental period, vascular reactivity to norepinephrine (NE), acetylcholine (ACh) and sodium nitroprusside (SNP) were assessed with or without the presence of L-nitro-arginine (LNA) or 4-Amino-pyridine (4AP).
 Results: Percent contractile response to NE was higher (p < 0.01) while relaxation response to ACh was lower in the SMK and NCT (p < 0.05) groups. LNA-induced inhibition to ACh was significantly reduced in both SMK and NCT groups. 4AP-induced inhibition to ACh was significantly increased only in the NCT group. 4AP-induced inhibition to SNP was increased in SMK group. NS oil reduced only contractile response to NE in NCT group. It also significantly improved relaxation response to ACh as well as restored LNA-induced inhibition to ACh in the SMK and NCT groups. Interestingly, while NS oil reduced 4AP-induced inhibition in the NCT group, it reduced 4AP-induced inhibition to SNP in the SMK group.
 Conclusion: NS oil ameliorates vascular dysfunction by reducing contractile response in rats exposed to nicotine vapour while increasing endothelium-dependent relaxation as well as restoring differentially both LNA- and 4AP-induced inhibition in rats exposed to cigarette smoke and nicotine vapour.