Delivery Of Sodium Nitroprusside Research Articles

Real-time observation of aortic vessel dilation through delivery of sodium nitroprusside via slow release mesoporous nanoparticles

Spherical mesoporous nanoparticles (MNPs) with a diameter of ∼100nm were synthesised via a sol-gel method in the presences of organic template (with and without fluorescein dye encapsulation). The template molecules were removed by acidic extraction to form a regular pore lattice structure. The nanoparticle size and morphology were analysed using transmission electron microscopy and dynamic light scattering analysis. The MNPs were further characterised by zeta potential, nitrogen adsorption measurements and infra-red spectroscopy. The interior pores had an average diameter of ∼3nm and were loaded with an endothelial-independent vasodilator, sodium nitroprusside (SNP). The optimal drug loading and drug release was determined in high potassium physiological salt solution using dialysis and atomic absorption spectroscopy. We demonstrate that the initial instantaneous release is due to the surface desorption of the drug followed by diffusion from the pores. Furthermore, these drug loaded MNPs (with and without fluorescein dye encapsulation) were added to viable aortic vessels and release in real-time was observed, ex vivo. MNPs and loaded with and without SNP were incubated with the vessel (at 1.96×1012NPmL−1) over a 3h time period. The real-time exposure to unloaded MNPs resulted in a small attenuation in constriction that occurred after approximately 1h. In contrast, MNPs loaded with SNP led to a rapid relaxation of aortic vessels that was sustained over the 3h period (p<0.001).

Responses of the skin microcirculation to acetylcholine and to sodium nitroprusside in chronic uremic patients

The aim of the present study was to assess the endothelial function of the microcirculation in chronic renal failure. We investigated the responses of the cutaneous blood flow to locally delivered acetylcholine and sodium nitroprusside in uremic patients. The study included 60 chronic uremic patients: 40 patients with a creatinine clearance of 4-25 ml/min were on conservative treatment and 20 patients were on maintenance hemodialysis. The changes in skin blood flow following iontophoretic delivery of acetylcholine (an endothelium-dependent vasodilator) and sodium nitroprusside (an endothelium-independent vasodilator) were measured by laser Doppler flowmetry. Acetylcholine induced a progressive increase in blood flow in both groups, reaching approximately 100% of the maximal hyperemic response obtained by sodium nitroprusside delivery. The percent increase in blood flow from baseline was lower in hemodialysis patients than in patients on conservative treatment, after both acetylcholine (550 +/- 44 vs. 718 +/- 61%, P < 0.05) and sodium nitroprusside (553 +/- 46 vs. 735 +/- 69%, P < 0.05) delivery. In the hemodialysis group, the hyperemic responses to acetylcholine and sodium nitroprusside did not improve after the hemodialysis session. Hence, the hyperemic responses of the skin microcirculation are lower in hemodialysis patients than in patients on conservative treatment, and did not ameliorate after hemodialysis. It seems to be independent of endothelial dysfunction, and associated with the severity of uremia and with the maintenance hemodialysis treatment. This microcirculatory abnormality is in keeping with the arterial stiffness and vascular wall damages described in dialysis patients, which contribute to the cardiovascular morbidity of chronic uremia.

Responses of the Skin Microcirculation to Acetylcholine in Patients with Essential Hypertension and in Normotensive Patients with Chronic Renal Failure

Aims: To assess the endothelial function of the skin microcirculation in chronic renal failure (CRF) independent of hypertension, we investigated the changes of the cutaneous blood flow induced by iontophoretic delivery of acetylcholine (ACh) and of sodium nitroprusside (SNP) in CRF patients free from arterial hypertension and in patients with essential hypertension. Methods: The study included 20 patients affected by CRF (mean creatinine clearance 12 ± 2 ml/min) without arterial hypertension (mean blood pressure 96 ± 1 mm Hg), 15 patients affected by essential hypertension (mean blood pressure 124 ± 1 mm Hg), and 20 normal controls. The changes of skin blood flow following iontophoretic delivery of ACh and of SNP were measured by laser Doppler flowmetry. Results: Following maximal ACh or SNP delivery, the change of blood flow from the baseline was similar both in normals (683 ± 92 vs. 684 ± 87%) and in CRF patients (778 ± 108 vs. 803 ± 124%), whereas in the hypertensives the response to ACh was lower than to SNP (434 ± 48 vs. 702 ± 98%, p < 0.01). Since the third ACh delivery dose, the skin blood flow increments were significantly lower in the hypertensive than in the CRF or in the normal control groups, whereas no difference was observed between uremics and controls. Conclusions: The endothelium-dependent hyperemia following ACh iontophoretic delivery is impaired in the skin microcirculation of essential hypertensive patients, but this is not the case in CRF patients with no history of arterial hypertension. This suggests that CRF per se, independent of arterial hypertension, is not associated with endothelial dysfunction of skin microcirculation.