Tiodazosin, a new antihypertensive, resembles prazosin in structure and alpha-adrenergic-blocking activity, and it also exerts a direct vasodilator effect. We evaluated its long-term hemodynamic and systemic effects in patients with essential hypertension. Our data show that after 10 wk of therapy with tiodazosin, 7 of our 10 patients had significant reduction in intra-arterial mean blood pressure as a result of a fall in systemic vascular resistance. Heart rate, cardiac output, and plasma volume did not change. Systemic effects were minor and included a gain in weight and a reduction in hemoglobin, hematocrit, platelet count, serum protein, albumin, bilirubin, and specific gravity of urine. No patient initially developed orthostatic symptoms after the first dose, but there were transient episodes of light-headedness in three patients, palpitations in two, increased urinary frequency in one, and drooping of eyelid in another during the trial period. One patient developed profound orthostatic hypotension, which could be attributed to the drug. Because of such side effects and the failure to lower blood pressure in 30% of patients with essential hypertension, tiodazosin appears to have several important drawbacks and little advantage over currently available antihypertensives.
It is unclear whether the stiffened arterial tree in systolic hypertension is the cause or the effect of the disease. In this study, brachial and radial arterial pulses were sensed by external Pixie transducers and measurements of pulse wave velocity converted to volume distensibility using the Bramwell-Hill equation. Blood pressure was controlled as a variable by repeating the measurements at a variety of transmural arterial pressures. This was accomplished by encasing the forearm in a rigid plastic cylinder within which pressures were varied. Twenty-nine patients with systolic hypertension were compared with 22 age-matched control subjects. At ambient pressures the volume distensibility of patients was lower than that of control subjects (0.10 versus 0.18% delta volume/mm Hg, p less than 0.001) but there was no difference in volume distensibility between the two groups at any comparable transmural pressure. Nineteen patients were treated for 1 month with a thiazide diuretic agent and the studies were then repeated. Systolic and diastolic blood pressure decreased significantly and volume distensibility increased (0.10 to 0.15% delta volume/mm Hg, p less than 0.001) at ambient pressures. But at comparable transmural pressures, volume distensibility was unchanged. It is concluded that, in the forearm, increased arterial stiffness is the result and not the cause of systolic hypertension, but these data cannot exclude increased aortic stiffness as a significant factor. Thiazide diuretic drugs increase forearm arterial compliance by lowering blood pressure without a demonstrable drug effect on this arterial wall.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.