Effects of morphine on reflex arteriolar constriction induced in man by hypercapnia

Robert Zelis, Stephen F. Flaim, John H. Eisele

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Since morphine alters ventilatory drive during chemoreceptor stimulation, we have examined whether it produces a similar resetting of the hypercapnia-induced arteriolar constrictor reflex. In 11 normal subjects, forearm blood flow (FBF) was measured plethysmographically and forearm vascular resistance (FVR) was calculated before and during hypercapnia induced by a rebreathing technique. An increase in arterial carbon dioxide tension (PaCO2) (16.8 ± 1.1 mm Hg) increased FVR by 30.5 ± 4.8 mm Hg/ml/min · 100 ml (55.1 ± 5.1 to 85.6 ± 9.0). Fifteen minutes after intravenous administration of 15 mg of morphine sulfate (MS), a similar increase in PaCO2 (16.6 ± 1.2 mm Hg) caused an increase in FVR of 16.7 ± 3.9 mm Hg/ml/min · 100 ml (34.1 ± 4.1 to 50.8 ± 6.7). The change in FVR with CO2 during MS was less than that before MS (p < 0.02). When the sequential response patterns to CO2 challenge were determined, it was found that, prior to MS, the FVR increase occurred as a late response to hypercapnia, but after MS the late increase in FVR did not occur and in several subjects there was a general tendency toward net vasodilation. An MS-induced resetting of the constrictor reflex mechanism to CO2 must therefore have tended to unmask the direct dilator properties of the CO2. Such a dilation caused by hypercapnia and unopposed by the normal reflex mechanism may partially explain the hypotensive effect of MS when administered to susceptible patients with CO2 retention. The attenuated chemoreceptor reflex-induced arteriolar constriction due to CO2 stimulation may also explain the withdrawal of alpha adrenergic tone which occurs when MS is given to normal subjects. This alteration in the chemoreceptor reflex mechanism may occur at the level of the central nervous system since naloxone effectively restored the reflex response to normal.

Original languageEnglish (US)
Pages (from-to)172-178
Number of pages7
JournalClinical pharmacology and therapeutics
Volume22
Issue number2
DOIs
StatePublished - Aug 1977

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

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