Pial arterial response to topical verapamil in acute closed cranial windows in rabbits.
We have previously observed that intraarterial verapamil increases cerebral blood flow, whereas nitric oxide donors, such as nitroglycerin, do not. Clinically, both verapamil and nitroglycerin dilate large cerebral arteries. Therefore, we hypothesized that topical verapamil would dilate both the large proximal and the small distal cerebral arteries, whereas nitroglycerin would preferentially dilate only the large proximal arteries. We tested our hypothesis in acute cranial windows implanted in 10 New Zealand White rabbits. After predrug measurements, we superfused 4 increasing concentrations of verapamil or nitroglycerin (10(-8), 10(-6), 10(-4), and 10(-3) M) in the cranial windows for 5 min each. The maximum increase in diameter was expressed as a percentage change from predrug diameters. There was a 30-min period of rest between the two drug challenges. Topical verapamil increased the arterial diameter of the larger proximal arterioles (>60 microm) by 32% +/- 18% and that of the smaller distal arterioles (<60 microm) by 62% +/- 42%. A modest increase in arterial diameters of 11% +/- 11% was observed after topical nitroglycerin that was significant only for the large-proximal arterioles. Within the 10(-8) to 10(-3) M range, topical verapamil, compared with nitroglycerin, proved to be a more potent cerebral vasodilator and had a more robust vasodilator effect on the distal small pial arteries.
Hartl
Roger
R
*Department of Neurosurgery, Weill Medical College, Cornell University, New York, New York; and Departments of †Anesthesiology, ‡Neurological Surgery, and §Internal Medicine, College of Physicians and Surgeons, Columbia University, New York, New York.
Joshi
Shailendra
S
Levine
Sean
S
Wang
Mei
M
Sciacca
Robert R
RR
D000287:Administration, Topical; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002245:Carbon Dioxide / Q000378:metabolism; D002536:Cerebral Arteries / Q000187:drug effects*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003399:Craniotomy; D005260:Female; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology; D011817:Rabbits; D013238:Stereotaxic Techniques; D014665:Vasodilator Agents / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D014665:Vasodilator Agents; D002245:Carbon Dioxide; D014700:Verapamil; D005996:Nitroglycerin