Calcium channel blockers induce preferential coronary vasodilation by an alpha 1-mechanism.
The effects of nitrendipine were evaluated on coronary and systemic dynamics in conscious dogs. Nitrendipine (8 micrograms X kg-1 X min-1) decreased late diastolic left circumflex coronary resistance (62 +/- 1.3%) significantly more (P less than 0.01) than total peripheral resistance (54 +/- 1.8%). After propranolol (1 mg/kg) and atropine methyl bromide (0.1 mg/kg) to eliminate reflex increases in myocardial metabolic demand, nitrendipine still reduced late diastolic coronary resistance (56 +/- 1.5%) significantly more (P less than 0.01) than total peripheral resistance (46 +/- 1.4%). However, after adding alpha 1-adrenergic receptor blockade with prazosin (1 mg/kg) to beta-adrenergic and cholinergic receptor blockades, nitrendipine no longer reduced late diastolic coronary resistance (40 +/- 2.7%) more than total peripheral resistance (45 +/- 2.1%) and, in fact, reduced late diastolic coronary resistance less than prior to prazosin. Nifedipine and diltiazem also reduced late diastolic coronary resistance more than total peripheral resistance prior to, but not after, alpha 1-adrenergic receptor blockade. In contrast, sodium nitroprusside reduced late diastolic coronary resistance more (P less than 0.01) than total peripheral resistance both before and after alpha 1-adrenergic receptor blockade. Thus calcium channel blockers preferentially dilate the coronary bed in comparison with the systemic circulation. Since the preferential effects were abolished by prazosin, an alpha 1-adrenergic mechanism is implicated.
Knight
D R
DR
Vatner
S F
SF
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002302:Cardiac Output / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects*; D004285:Dogs; D010276:Parasympatholytics / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D002121:Calcium Channel Blockers; D010276:Parasympatholytics; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta