The present study explores the contribution of alterations in resting tone to cerebral artery narrowing in SHRs (spontaneously hypertensive rats) and the role of hypertension development. Young pre-hypertensive and adult fully hypertensive SHRs and age-matched Wistar-Kyoto rat controls were used. The contribution of basal vasoactive factors to resting tone was studied in middle cerebral arteries with pressure myography. Basal NO and O(2)(-) (superoxide anion) availability were determined with fluorescent indicators using confocal microscopy and lucigenin-enhanced chemiluminescence. Basal O(2)(-) was also assessed in mesenteric resistance arteries. Middle cerebral arteries from adult rats, but not young pre-hypertensive rats, had augmented myogenic responses and resting tone and decreased relaxation to sodium nitroprusside compared with their normotensive counterparts. Cerebral arteries from adult SHRs also had an increase in tonic NO associated with a decrease in basal O(2)(-) availability. Basal O(2)(-) was instead increased in mesenteric arteries from SHRs. The present results indicate that large cerebral arteries from SHRs have an increase in their resting tone as a consequence of sustained hypertension and that this is related to a decrease in NO responsiveness. We suggest that this increase in resting tone and myogenic responses could act as a protective mechanism against the development of stroke in SHRs. The present study also demonstrates some unusual findings regarding the current understanding of the NO/O(2)(-) balance in hypertension with important differences between vascular beds and draws attention to the complexity of this balance in cardiovascular health and disease.