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Propranolol in conscious spontaneously hypertensive rats

I. Cardiovascular effects after subcutaneous and intracerebroventricular administration

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Summary

The time course of the effects of varying doses of dl-propranolol on isoprenaline induced tachycardia and hypotension, as well as the effects of propranolol on mean arterial pressure and heart rate were studied in conscious spontaneously hypertensive rats (SHR) both after subcutaneous (s.c.) and intracerebroventricular (i.c.v.) administration.

  1. 1.

    The degree of inhibition of isoprenaline-induced tachycardia and hypotension was dose dependent, maximal inhibition being observed 30 min after both s.c. and i.c.v. injection of propranolol. Inhibition was similar for s.c. and i.c.v. injection.

  2. 2.

    Bradycardia developed immediately, a maximum being reached 10–30 min after s.c. administration of 0.04–5 mg/kg propranolol. Heart rate returned to control levels 1–4 h after injection. Effects of s.c. and i.c.v. administered propranolol were of similar magnitude.

  3. 3.

    During the first 1–2 h after injection the only effect observed on mean arterial pressure was a slight but significant increase, which was most pronounced after the highest dose injected i.c.v. (1 mg/kg).

  4. 4.

    After the initial increase in mean arterial pressure a hypotensive effect developed slowly, reaching maximum 8–12 h after s.c. injection. Hypotension was still observed 20 h after injection.

It is concluded that there is a dissociation between the time course of effects of propranolol on beta-adrenoceptors and heart rate on the one hand and mean arterial pressure on the other. The reason for the delayed antihypertensive effect is still unclear. Furthermore, it is concluded that i.c.v.-injected propranolol rapidly leaks to the peripheral bloodstream, thereby causing effects through a peripheral action.

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Authors and Affiliations

  1. Department of Pharmacology, Rijksuniversiteit Limburg, Beeldsnijdersdreef 101, NL-6200 MD, Maastricht, The Netherlands

    J. F. M. Smits, H. van Essen & H. A. J. Struyker-Boudier

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  1. J. F. M. Smits
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  2. H. van Essen
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  3. H. A. J. Struyker-Boudier
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Smits, J.F.M., van Essen, H. & Struyker-Boudier, H.A.J. Propranolol in conscious spontaneously hypertensive rats. Naunyn-Schmiedeberg's Arch. Pharmacol. 309, 13–18 (1979). https://doi.org/10.1007/BF00498751

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  • DOI: https://doi.org/10.1007/BF00498751

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