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Differential effects of intracoronary versus intravenous nifedipine on myocardial blood flow and function distal to a severe coronary artery stenosis
28 ALRENAL STERJIDS AND PRBSSDRE-INDUCED LEFT VBt?l’RIC!HLAR HYPERTRGPKY. Norberto C. Gonzalez, Vicki Donoso and Michael D. Bailie. Depts. of Physiology and Pediatrics. University of Kansas Medical Center, Kansas City, Kansas, 66103. Adrenalectany (Adx) reduces the left ventricular hypertrophy (LVH) secondary to abdominal aortic coarctation (AC) in rats. This is due to absence of the cortex and not due to a different blood pressure response to AC in Adx rats. The objective of these experiments was to determine if aldosterone administration to Adx rats could alter the development of LVH after AC. Six groups of adult, male Sprague Dawley rats were used: Group 1: Intact, AC: Group 2: Intact sham coarctad (SC); Group 3: Adx, AC: Group 4: Adx, SC; Group 5: Adx, AC + Aldosterone (20 m/h for 12 days): Group 6: Adx, SC + Aldosterone. Aldosterone was delivered with osmotic minipumps. All animals were sacrificed 12 days after AC or SC. Groups 1, 3 and 5 showed similar systemic hypertension. Left wntricular weight was 60% higher in group 1 than in group 2, but only 23% higher in group 3 than in group 4. Aldosterone did not appreciably alter the LVH response to AC: left ventricular weight was 30% higher in group 5 than in group 6. This suggests that maintenance of normal serum aldosterone in Adx rats did not affect LVH response to AC. However, a transitory stimulation of the renin-angiotensinaldosterone system occurs shortly after AC in intact rats. These experiments do not rule out a possible role of a transitory increase in aldosterone in LVH developnent. Supported by American Heart Association and National Institutes of Health.
ANALYSIS OF THE PERIPHERAL VASCULAR ACTIONS OF ASL-7022, A NOVEL CATECHOLAMINE. R. J. Gorczynski and R. D. Reynolds, Department of Pharmaceutical Research, American Critical Care, McGaw Park, Illinois 60085, U.S.A. The peripheral vascular actions of intravenously administered ASL-7022 were investigated in isolated hindlimbs of normal, acute baroreceptor-denervated (ABD) and spinal, anesthetized dogs. In normal animals, ASL-7022 produced vasodilation. Propranolol (1.0 mg/kg, i.v.) reduced but did not eliminate vasodilation in these preparations but combined beta-adrenergic and ganglionic blockade converted responses to vasoconstriction. ASL-7022 induced greater vasodilation in ABD animals than in normal animals; in ABD preparations propranolol partially blocked vasodilation, ganglionic blockade eliminated vasodilation and beta-adrenergic and ganglionic blockade converted responses to vasoconstriction. In spinal dogs ASL-7022 induced slight vasoconstriction (low doses) and slight dilation (high doses). The compound caused only vasoconstriction in propranolol pretreated hindlimbs and only vasodilation in phentolamine pretreated hindlimbs of spinal animals. ASL-7022 dose-dependently inhibited vasoconstrictor responses to electrical stimulation of the lumbar sympathetic chain in spinal dogs. The data suggest that ASL-7022 possesses at least three vascular effects: 1) neurogenic vasodilation due to interruption of sympathetic neurotransmission, 2) vasodilation due to vascular beta-adrenergic receptor activatior and 3) vasoconstriction due to vascular alpha-adrenergic receptor activation.
DIFFERENTIAL EFFECTS OF INTRACORONARY VERSUS INTRAVENOUS NIFEDIPINE ON MYOCARDIAL BLOOD FLOW AND FUNCTION DISTAL TO A SEVERE CORONARY ARTERY STENOSIS. Garrett J. Gross, David C. Warltier, Harold F. Hardman and Kathryn A. Lamping. Department of Pharmacology and Toxicology, The Medical College of Wisconsin, Milwaukee, Wisconsin 53226. The purpose of the present study was to differentiate the direct myocardial effects from the indirect peripheral effects of nifedipine on regional myocardial blood flow and contractile function distal to a severe coronarv arterv stenosis in anesthetized dogs. Nifedipine was administered intracoronary (10 pg)*or intravenously (0.5-1.0 ug/kq/min). Mwcardial seoment lenath (% SS) and blood flow were measured with uitrasonic crystals and radioactive mi.crospheres, respectively. Intravenous nifedipine resulted in an increase in ischemic contractility (3.0 f 2.6 to 7.4 f 2.3 % SS) whereas intracoronary nifedipine produced a decrease in function (7.5 f 1.5 to (-) 1.04 f 3.2 % SS) of the ischemic zone. Nifedipine did not affect blood flow to the ischemic area by either route of administration. In conclusion, nifedipine appears to improve ischemic myocardial function via its indirect peripheral vasodilatory actions and not by a direct effect on the ischemic myocardium. (Supported by USPHS Grant HL 08311).
ANALYSIS OF THE PERIPHERAL VASCULAR ACTIONS OF ASL-7022, A NOVEL CATECHOLAMINE. R. J. Gorczynski and R. D. Reynolds, Department of Pharmaceutical Research, American Critical Care, McGaw Park, Illinois 60085, U.S.A. The peripheral vascular actions of intravenously administered ASL-7022 were investigated in isolated hindlimbs of normal, acute baroreceptor-denervated (ABD) and spinal, anesthetized dogs. In normal animals, ASL-7022 produced vasodilation. Propranolol (1.0 mg/kg, i.v.) reduced but did not eliminate vasodilation in these preparations but combined beta-adrenergic and ganglionic blockade converted responses to vasoconstriction. ASL-7022 induced greater vasodilation in ABD animals than in normal animals; in ABD preparations propranolol partially blocked vasodilation, ganglionic blockade eliminated vasodilation and beta-adrenergic and ganglionic blockade converted responses to vasoconstriction. In spinal dogs ASL-7022 induced slight vasoconstriction (low doses) and slight dilation (high doses). The compound caused only vasoconstriction in propranolol pretreated hindlimbs and only vasodilation in phentolamine pretreated hindlimbs of spinal animals. ASL-7022 dose-dependently inhibited vasoconstrictor responses to electrical stimulation of the lumbar sympathetic chain in spinal dogs. The data suggest that ASL-7022 possesses at least three vascular effects: 1) neurogenic vasodilation due to interruption of sympathetic neurotransmission, 2) vasodilation due to vascular beta-adrenergic receptor activatior and 3) vasoconstriction due to vascular alpha-adrenergic receptor activation.
DIFFERENTIAL EFFECTS OF INTRACORONARY VERSUS INTRAVENOUS NIFEDIPINE ON MYOCARDIAL BLOOD FLOW AND FUNCTION DISTAL TO A SEVERE CORONARY ARTERY STENOSIS. Garrett J. Gross, David C. Warltier, Harold F. Hardman and Kathryn A. Lamping. Department of Pharmacology and Toxicology, The Medical College of Wisconsin, Milwaukee, Wisconsin 53226. The purpose of the present study was to differentiate the direct myocardial effects from the indirect peripheral effects of nifedipine on regional myocardial blood flow and contractile function distal to a severe coronarv arterv stenosis in anesthetized dogs. Nifedipine was administered intracoronary (10 pg)*or intravenously (0.5-1.0 ug/kq/min). Mwcardial seoment lenath (% SS) and blood flow were measured with uitrasonic crystals and radioactive mi.crospheres, respectively. Intravenous nifedipine resulted in an increase in ischemic contractility (3.0 f 2.6 to 7.4 f 2.3 % SS) whereas intracoronary nifedipine produced a decrease in function (7.5 f 1.5 to (-) 1.04 f 3.2 % SS) of the ischemic zone. Nifedipine did not affect blood flow to the ischemic area by either route of administration. In conclusion, nifedipine appears to improve ischemic myocardial function via its indirect peripheral vasodilatory actions and not by a direct effect on the ischemic myocardium. (Supported by USPHS Grant HL 08311).