Vasodilating effect of the new β-blocker tilisolol hydrochloride in humans

The effects of a new β-blocker, (±)-4-(3-tert-butylamino-2-hydroxypropoxy)-2-methyl-1(2H)-isoquinoli none hydrochloride (tilisolol hydrochloride, N-696), on forearm circulation were examined and compared with those of propranolol in healthy young males. N-696 (30 mg/d for 7 days) decreased heart rate from 75 ± 4 to 56 ± 2 bpm (p < 0.01) and decreased mean blood pressure from 86 ± 2 to 79 ± 2 mmHg (p < 0.05) (n = 7). Propranolol (60 mg/d for 7 days) decreased heart rate from 62 ± 1 to 51 ± 2 (p < 0.01) and decreased mean blood pressure from 83 ± 3 to 73 ± 3 mmHg (p < 0.01) (n = 7). Resting forearm blood flow and forearm vascular resistance were not altered by N-696, whereas propranolol decreased forearm blood flow (p < 0.05) and increased forearm vascular resistance (p < 0.01). Reflex forearm vasoconstriction was examined by measuring forearm vascular resistance with a strain gauge plethysmograph during lower body negative pressure (LBNP). The regression line relating central venous pressure and forearm vascular resistance during LBNP was shifted toward the resistance axis by propranolol but was not altered by N-696. Propranolol augmented forearm vascular responses to intraarterially infused norepinephrine but N-696 did not alter them. Thus, in contrast to propranolol, N-696 lowered blood pressure and heart rate without peripheral vasoconstriction and did not augment forearm vasoconstrictive responses to norepinephrine.