{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T21:00:41Z","timestamp":1772917241450,"version":"3.50.1"},"reference-count":53,"publisher":"American Physiological Society","issue":"6","funder":[{"name":"Yahel Foundation","award":["none"],"award-info":[{"award-number":["none"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"published-print":{"date-parts":[[2017,6,1]]},"abstract":"<jats:p>Cerebrovascular CO<jats:sub>2<\/jats:sub>reactivity is affected by nitric oxide (NO). We tested the hypothesis that sildenafil selectively potentiates NO-cGMP signaling, which affects CO<jats:sub>2<\/jats:sub>reactivity. Fourteen healthy males (34\u2009\u00b1\u20092 yr) were enrolled in the study. Blood pressure (BP), ECG, velocity of cerebral blood flow (CBF; measured by transcranial Doppler), and end-tidal CO<jats:sub>2<\/jats:sub>(EtCO<jats:sub>2<\/jats:sub>) were assessed at baseline (CO<jats:sub>2<\/jats:sub>~39 mmHg), during hyperventilation (CO<jats:sub>2<\/jats:sub>~24 mmHg), during hypercapnia (CO<jats:sub>2<\/jats:sub>~46 mmHg), during boluses of phenylephrine (25\u2013200 \u00b5g), 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 EtCO<jats:sub>2<\/jats:sub>: 117\u2009\u00b1\u20092\/67\u2009\u00b1\u20093 mmHg, 69\u2009\u00b1\u20093 beats\/min, 84\u2009\u00b1\u20095 and 57\u2009\u00b1\u20094 cm\/s, 1.56\u2009\u00b1\u20090.1 mmHg\u00b7cm<jats:sup>\u22121<\/jats:sup>\u00b7s<jats:sup>\u22121<\/jats:sup>, 14\u2009\u00b1\u20090.5 breaths\/min, and 39\u2009\u00b1\u20090.9 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\u2009\u00b1\u20092 vs. 20\u2009\u00b1\u20092% ( P &lt; 0.05) and increased the eCVR, 2.5\u2009\u00b1\u20090.2 vs. 2\u2009\u00b1\u20090.2% ( P &lt; 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 CO<jats:sub>2<\/jats:sub>reactivity without affecting the static and dynamic pressure-dependent mechanisms of cerebrovascular autoregulation.<\/jats:p>","DOI":"10.1152\/ajpregu.00241.2016","type":"journal-article","created":{"date-parts":[[2017,3,30]],"date-time":"2017-03-30T01:10:37Z","timestamp":1490836237000},"page":"R948-R955","source":"Crossref","is-referenced-by-count":13,"title":["Nitric oxide-sensitive guanylyl cyclase signaling affects CO<sub>2<\/sub>-dependent but not pressure-dependent regulation of cerebral blood flow"],"prefix":"10.1152","volume":"312","author":[{"given":"Shadi","family":"Jahshan","sequence":"first","affiliation":[{"name":"J. 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