Nitric oxide (NO) released from NO donors has hypotensive effect and it induces rat aorta relaxation due to the activation of K+ channels, guanylyl‐cyclase and SERCA

Abstract

NO reduces cytosolic Ca+2 in the vascular smooth muscle cells by cGMP‐PKG, K+ channels activation and Ca+2 uptake via sarcoplasmic reticulum Ca‐ATPase (SERCA). This study aimed to investigate if NO released from PY and SNP activates K+ channels and the enzymes guanylyl‐cyclase (GC) and SERCA. We also studied its effect on the mean arterial pressure (MAP). Vascular reactivity to PY and SNP were studied in denuded rat aortic rings pre‐contracted with phenylephrine (Phe). Concentration‐effect curves for PY and SNP were constructed with or without the inhibitors of GC (ODQ 1μM), SERCA (Thapsigargin, TG 1μM) and K+ channel (TEA 1mM). MAP was recorded in conscious hypertensive rats after in bolus injection of PY (5, 7mg/Kg) or SNP (35μg/Kg). PY induced hypotensive effect at the doses of 5 mg/Kg (−18.3 ±3.8 mmHg) and 7mg/Kg (−24±4mmHg) which effects were lower but longer (10.4min) than SNP 35μg/Kg (−80±6.1, 1.18min). PY and SNP presented similar efficacy in inducing aortic ring relaxation, but PY (pD2: 6.5±0.1) was less potent (pD2) than SNP (pD2: 8.07±0.1). The relaxation was inhibited by ODQ (PY: 37.9±3.6%, SNP: 29.3±2.6%) and TG (pD2: PY 5.7±0.2, SNP: 7.69±0.1). However, TEA reduced the relaxation to PY (pD2: 5.8±0.1) but it had no effect on SNP. In conclusion, NO released from PY has hypotensive effect and it induces relaxation due to the activation of K+ channels, sGC and SERCA. Supported by Fapesp and CNPq.