Nitric oxide-sensitive guanylyl cyclase signaling affects CO2-dependent but not pressure-dependent regulation of cerebral blood flow

Cerebrovascular CO2 reactivity is affected by nitric oxide (NO). We tested the hypothesis that sildenafil selectively potentiates NO-cGMP signaling, which affects CO2 reactivity. Fourteen healthy males (34 +/- 2 yr) were enrolled in the study. Blood pressure (BP), ECG, velocity of cerebral blood flow (CBF; measured by transcranial Doppler), and end-tidal CO2 (EtCO2) were assessed at baseline (CO2 similar to 39 mmHg), during hyperventilation (CO2 similar to 24 mmHg), during hypercapnia (CO2 similar to 46 mmHg), during boluses of phenylephrine (25-200 mu g), and during graded head-up tilting (HUT). Measurements were repeated 1 h after 100 mg sildenafil were taken. Results showed that sildenafil did not affect resting BP, heart rate, CBF peak and mean velocities, estimated regional cerebrovascular resistance (eCVR; mean BP/mean CBF), breath/min, and EtCO2: 117 +/- 2/67 +/- 3 mmHg, 69 +/- 3 beats/min, 84 +/- 5 and 57 +/- 4 cm/s, 1.56 +/- 0.1 mmHg.cm(-1).s(-1), 14 +/- 0.5 breaths/min, and 39 +/- 0.9 mmHg, respectively. Sildenafil increased and decreased the hypercapnia induced in CBF and eCVR, respectively. Sildenafil also attenuated the decrease in peak velocity of CBF, 25 +/- 2 vs. 20 +/- 2% (P < 0.05) and increased the eCVR, 2.5 +/- 0.2 vs. 2 +/- 0.2% (P < 0.03) during hyperventilation. Sildenafil did not affect CBF despite significant increases in the eCVRs that were elicited by phenylephrine and HUT. This investigation suggests that sildenafil, which potentiates the NO-cGMP signaling, seems to affect the cerebrovascular CO2 reactivity without affecting the static and dynamic pressure-dependent mechanisms of cerebrovascular autoregulation.