Threshold Dosages of Nitroglycerin for Coronary Artery Dilatation, Afterload Reduction,and Venous Pooling in Conscious Dogs

Bassenge, E.; Holtz, J.; Kinadeter, H.; Kolin, Alexander

doi:10.1007/978-3-642-68085-4_37

Cited by 12 publications

(2 citation statements)

References 28 publications

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“…i, 19,21 Before autonomic blockade, the arterial pressure in the tolerant state (under ongoing nitroglycerin infusion) was not lower than that of the same dogs in the nontolerant state (no ongoing nitroglycerin), apparently indicating tolerance of arterial pressure to nitroglycerin ( figure 6). This dose of nitroglycerin (1.5 ,rg/kg/ min) is below that usually described as the threshold for arteriolar effects37 38 and did not result in a lowering of peripheral resistance in our conscious dogs in the nontolerant state (see Results: Validation experiments). However, at the same time, the rate of norepinephrine release was significantly increased in these conscious dogs (figure 8), indicating a compensatory increase in sympathetic activity.…”

Section: Methodsmentioning

confidence: 62%

Altered spectrum of nitroglycerin action in long-term treatment: nitroglycerin-specific venous tolerance with maintenance of arterial vasodepressor potency.

Stewart¹,

Elsner²,

Sommer³

et al. 1986

Circulation

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The study of venodilator tolerance to nitroglycerin has been complicated by reflex compensation and by problems in analyzing venous tone in the presence of multiple determinants of venous pressure. We assessed venous tone as total effective vascular compliance (TEVC) undei autonomic blockade in six dogs, in the nontolerant state, and during a 5 day infusion of nitroglycerin (1.5 ,ug/kg/min). Under long-term treatment, baseline TEVC was unaffected and the nitroglycerin dose-response relationship for TEVC was shifted to greater than 10-fold higher doses, whereas baseline mean arterial pressure (MAP) was lowered by 17 3 mm Hg without any shift in nitroglycerin responsiveness. This lowering of MAP was observed only after autonomic blockade. In six additional dogs instrumented with aortic flow probes, nitroglycerin (1.5 ,ug/kg/min) induced a 15 + 1% decline in peripheral vascular resistance (PVR) under autonomic blockade, but with reflexes intact these dogs showed no change in PVR and a 21 + 10% increase in norepinephrine release rate. We conclude that modest long-term exposure to nitroglycerin results in tolerance to its venodilating effects, whereas arteriolar action is maintained. This tolerance-induced shift in action from venous toward arteriolar dilation is normally masked by compensatory reflexes.

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Section: Methodsmentioning

confidence: 62%

Altered spectrum of nitroglycerin action in long-term treatment: nitroglycerin-specific venous tolerance with maintenance of arterial vasodepressor potency.

Stewart¹,

Elsner²,

Sommer³

et al. 1986

Circulation

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“…While the a/b-ratio is thought mainly to reflect changes in peripheral arterial resistance, the decrease in blood pressure, and in part also the increase in heart rate, during orthostasis following administration of nitrates is primarily the result of enhanced venous pooling. The latter effect is more sensitive to organic nitrates than their actions on the arterial side and it also exhibits a different concentration-effect relationship (Miller et al 1976;Imhof et al 1980;Bassenge et al 1981;Gerson et al 1982;Gwilt et al 1983). There may be some quantitative differences between nitrates with respect to their arterial and venous effects (Toyoda et al 1986;Ahlner et al 1991).…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and haemodynamic effects of ISDN following different dosage forms and routes of administration

Vogt

Trenk

Bonn

et al. 1994

Eur J Clin Pharmacol

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The pharmacokinetics and haemodynamic effects of isosorbide dinitrate (ISDN) have been investigated following administration of single doses as a sublingual (SL) spray (2.5 mg), sublingual tablet (5 mg) and peroral tablet (10 mg) in a randomised, placebo-controlled double-blind cross-over trial in 16 healthy volunteers. After the sublingual spray Cmax was higher (39.0 ng.ml-1) and tmax was shorter (3.9 min) than after the sublingual (22.8 ng.ml-1 and 13.8 min) and peroral (16.9 ng.ml-1 and 25.6 min) tablets. The AUC of ISDN did not differ following any of the three formulations (1031; 879; 997 ng.ml-1.min, for the spray, SL tablet and PO-tablet, respectively). Mononitrate metabolites of ISDN (IS-2-MN and IS-5-MN) and total nitrates in plasma increased in proportion to the administered dose. This indicates that the fraction of the dose absorbed was the same for all the formulations but that the extent of first-pass metabolism increased in the order sublingual spray < sublingual tablet < peroral tablet. Thus, compared to the spray, the relative bioavailability of ISDN was 48% and 28% from the sublingual and peroral tablets, respectively. The haemodynamic effects were quantified using the a/b ratio of the finger pulse wave and the systolic blood pressure and heart rate under orthostatic conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

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From the editor

Conti¹

1989

Clinical Cardiology

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Threshold Dosages of Nitroglycerin for Coronary Artery Dilatation, Afterload Reduction,and Venous Pooling in Conscious Dogs

Cited by 12 publications

References 28 publications

Altered spectrum of nitroglycerin action in long-term treatment: nitroglycerin-specific venous tolerance with maintenance of arterial vasodepressor potency.

Altered spectrum of nitroglycerin action in long-term treatment: nitroglycerin-specific venous tolerance with maintenance of arterial vasodepressor potency.

Pharmacokinetics and haemodynamic effects of ISDN following different dosage forms and routes of administration

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