The effect of nitric oxide inhibitors and s-nitrosothiols on hemodynamic parameters in an animal model

Sophia Bryan¹, Ruby Alexander-Lindo¹, Tara Dasgupta², Donovan McGrowder^3
1Department of Basic Medical Sciences, Faculty of Medical Sciences, ²Department of Chemistry, Faculty of Pure and Applied Sciences, ³Department of Pathology, Faculty of Medical Sciences, University of the West Indies, Kingston, Jamaica

Background: Nitric oxide (NO) is becoming an increasingly important signaling molecule implicated in a growing number of physiological and pathophysiological processes. We sought to test the hypothesis that co-administration of S-nitro-N-acetylpenicillamine (SNAP) or S-nitrosocaptopril (CapSNO) with N^G-methyl-L-arginine ester (L-NAME) or N^G-methyl-L-arginine acetate (L-NMMA) may reverse the elevated systolic, diastolic, and mean arterial pressures caused by the administration of L-NAME or L-NMMA only.
Materials and methods: Blood pressure was measured using the CODA 6 machine. The hemodynamic parameters systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and heart rate (HR) were determined for each rat group. There was intravenous (IV) administration of the control (0.3 mL, saline) or dosage of 12.5 mg/kg body weight of SNAP or CapSNO via IV.
Results: In CapSNO and L-NAME-treated rats, CapSNO significantly decreased SBP from 131.12 ± 4.29 mmHg to 121.42 ± 4.24 mmHg after 5 minutes (P < 0.0001), and then L-NAME (administered at t = 5 min) increased SBP to 165.29 ± 6.79 mmHg at 10 minutes (P < 0.05). In SNAP and L-NAME-treated rats, SNAP significantly decreased SBP from 135.86 ± 2.84 mmHg to 106.98 ± 1.99 mmHg (P < 0.0001) after 5 minutes, and L-NAME increased SBP to 146.18 ± 3.19 mmHg after 25.0 minutes (P < 0.05). In rats treated with SNAP and L-NAME, SNAP decreased DBP to 74.98 ± 2.49 mmHg (P < 0.0001) after 5 minutes while L-NAME increased DBP to 105.01 ± 2.60 mmHg after 25 minutes (P < 0.05). In SNAP and L-NAME treated group there was an increase in HR after the administration of SNAP (486.60 ± 30.82 at 0 minutes to 555.66 ± 32.37 beats min-1 at 5 minutes; P < 0.0001), followed by a decrease in HR to 336.90 ± 17.48 beats min-1 at 25 minutes (P <0.05) after the administration of L-NAME (at t = 5 min).
Conclusion: The data suggest that the actions of L-NAME and L-NMMA reversed the effects of NO released from SNAP or CapSNO. These drugs could be beneficial in the control of blood pressure in hypertensive patients.

Keywords: nitric oxide, N^G-methyl-L-arginine ester, N^G-methyl-L-arginine acetate, S-nitro-N-acetylpenicillamine, blood pressure, S-nitrosocaptopril