Topical Verapamil Research Articles

The topical application of verapamil and nifedipine lowers intraocular pressure in conscious rabbits

1. The time-course of the ocular effects of topical verapamil and nifedipine as well as the dose-response relationship, were studied in conscious, normotensive rabbits. 2. Both drugs caused a dose-dependent fall of intraocular pressure, which lasted 4 hr or more. 3. Log dose-response curves of both drugs show a similar peak response, but the potency of verapamil was greater than that of nifedipine. 4. A fall in the intraocular pressure in the untreated eye was also observed. 5. Verapamil and nifedipine induced a reduction of the tonographic outflow facility in the treated eye.

Vasomotion in cerebral microcirculation of awake rabbits.

Cerebral arterioles of unanesthetized rabbits equipped with chronically implanted cranial windows exhibited spontaneous rhythmic variation in vessel caliber characteristic of vasomotion. This variation was noted in all examined vessels. The vasomotion was independent of arterial blood pressure or respiration. The average frequency was 0.74 cycles/min and was independent of vessel size. The mean amplitude of the oscillations had a statistically significant inverse relationship to vessel diameter (r = 0.69). Vasodilation induced by arterial hypercapnia, topical adenosine, or topical acetylcholine had no significant effect on the frequency or amplitude of vasomotion. Anesthesia significantly reduced the frequency in arterioles of all sizes and markedly reduced amplitude in large arterioles. Topical verapamil resulted in a statistically significant reduction in frequency and in peak amplitude. Variations in vessel diameter occurred simultaneously in arterioles and their companion venules. We conclude that the cerebral microcirculation displays active vasomotion, which is significantly depressed by anesthesia or topical verapamil. The results also suggest that vasomotion is probably controlled by local factors.

Elevation of intraocular pressure by calcium channel blockers.

Topical administration of three different calcium channel blockers (verapamil hydrochloride, diltiazem hydrochloride, or nifedipine) increased intraocular pressure transiently in rabbits. Outflow facility and episcleral venous pressure were unchanged. Aqueous humor flow seemed to be increased 30 minutes after topical application of verapamil when estimated by the Goldmann equation or by changes in anterior chamber fluorescein-labeled dextran concentration. However, aqueous humor ascorbate concentrations and turnover of radioactive iodide did not differ from that in the untreated eye. Ocular blood volume was found to be increased after topical application of verapamil, which suggested vascular changes as a possible mechanism for the induced increase in IOP. Topical verapamil raised IOP in healthy human volunteers, but the elevation was less than observed in rabbits. Single oral doses of verapamil in rabbits or human beings had no effect on IOP.

Urinary concentration in the papillary collecting duct of the rat. Role of the ureter.

Urine was observed to flow intermittently in the collecting ducts of the extrarenal papilla of antidiuretic rats. The purpose of this investigation was to test Reinking and Schmidt-Nielsen's hypothesis that intermittent flow plays an important role in the production of maximally concentrated urine. Samples of collecting duct fluid were obtained from the base and tip of the papilla by micropuncture through the intact ureter. Fluid osmolality rose sharply from base, 894+/-120 mosmol/kg H(2)O(-1) (mean+/-SE), to tip, 1,667+/-114 (P<0.001), a distance of only 2 mm, and was due exclusively to reabsorption of water. After excision of the ureter, which abolished intermittent flow, osmolality fell modestly at the base to 723+/-82 mosmol/kg H(2)O(-1) (P < 0.02), but strikingly at the tip to 1,012+/-103 (P < 0.001). The pelvic ureter was paralyzed by topical verapamil and dimethylsulfoxide, which abolished intermittent flow. Osmolality of urine at the tip was not changed (1,959+/-184 mosmol/kg H(2)O(-1) before, vs. 1,957+/-126 after paralysis). The ureter was severed just beyond the papillary tip, a maneuver which preserved intermittent flow but abolished urinary reflux over the papilla. Urinary osmolality fell from 1,876+/-134 mosmol/kg H(2)O(-1) to 1,284+/-115 (P < 0.005). These findings demonstrate that when the ureter is intact, over half of the increase in urinary osmolality above isotonicity occurs in the terminal one-fourth of the medullary collecting duct and is due exclusively to water reabsorption (no net solute addition). It is the continuity of the ureter, rather than intermittent flow due to ureteral peristalsis, which is essential for the formation of a maximally concentrated urine.