Inhibition of noradrenergic neurotransmission by apomorphine and pergolide in the in situ autoperfused rat renal and superior mesenteric vascular beds
- 11 Downloads
In vitro studies have provided evidence that presynaptic dopamine receptors are present in the rat renal and superior mesenteric vascular beds. To confirm this in vivo, the effects of locally administered apomorphine and pergolide were studied in the in situ autoperfused renal and superior mesenteric vascular beds.
Local infusion of apomorphine (1 μg · kg−1 · min−1 for 5 min) or pergolide (1 μg · kg−1 · min−1 for 5 min) into either the renal or the superior mesenteric artery had no effect on perfusion pressure per se. In the renal vascular bed, the pressure response to electrical stimulation (4 Hz, 1 ms, supramaximal voltage) was reduced to 49.8±4.8% by apomorphine and to 54.8±2.7% by pergolide; in the mesenteric vascular bed, apomorphine reduced the pressure response to electrical stimulation (4 Hz, 1 ms, supramaximal voltage) to 53.8±2.9, pergolide to 52.0±1.8%. Increases of perfusion pressure in the renal and in the mesenteric vascular bed induced by locally administered noradrenaline were not modified by apomorphine or pergolide.
In both vascular beds, the inhibition of the stimulation-evoked pressure responses by apomorphine or pergolide was completely antagonized by local administration of the dopamine receptor antagonist haloperidol in a dose (1 μg · kg−1) which did not influence the inhibitory effect of the α2-adrenoceptor agonist UK-14,304; the α2-adrenoceptor antagonist rauwolscine, in a dose (100 μg · kg−1) which completely antagonized the inhibitory effect of UK-14,304, did not antagonize the inhibitory effects of apomorphine and pergolide.
Local administration of rauwolscine per se increased the pressure response to stimulation at 4 Hz in both vascular beds. In contrast, local administration of haloperidol did not influence the stimulation-evoked pressure response.
These results provide evidence for the presence of presynaptic, inhibitory dopamine receptors on sympathetic nerves in the rat renal and mesenteric vascular beds; these receptors could be involved in the blood pressure lowering effects of dopamine receptor agonists, such as apomorphine and pergolide.
Key wordsRat Presynaptic dopamine receptors Mesenteric Renal
Unable to display preview. Download preview PDF.
- Anwar N, Mason DFJ (1979) The action of dopamine on constrictor responses in the perfused rat mesenteric artery. Br J Pharmacol 66:479P-498PGoogle Scholar
- Anwar N, Mason DFJ (1981) Actions of dopamine and apomorphine on the vasoconstrictor response of perfused mesenteric arteries of mouse, rat and rabbit. J Pharm Pharmacol 33: 150–154Google Scholar
- Bogaert MG, Dupont AG, Lefebvre RA (1986) Evidence of presynaptic dopamine receptors in the in situ perfused rat kidney. Br J Pharmacol 87 (Suppl):25PGoogle Scholar
- Buylaert WA, Willems JL (1976) Effects of apomorphine on vena saphena lateralis strips of the dog. Arch Int Pharmacoldyn 223:162–163Google Scholar
- Cambridge D (1981) UK 14,304, a potent and selective α2-agonist for the characterisation of α-adrenoceptor subtypes. Eur J Pharmacol 72:413–415Google Scholar
- Cavero I (1982) Effects of pergolide, a dopamine receptor agonist, and clonidine on cardiovascular responses evoked by activation of peripheral sympathetic outflow in rats. Clin Exp Hypertens [A] 4:221–233Google Scholar
- Cavero I, Lefevre-Borg F, Gomeni R (1981) Blood pressure lowering effects of N,N-di-n-propyldopamine in rats: Evidence for stimulation of peripheral dopamine receptors leading to inhibition of sympathetic tone. J Pharmacol Exp Ther 218:515–524Google Scholar
- Cavero I, Lefevre-Borg F, Lhoste F, Sabatier C, Richer C, Giudicelli JF (1984) Pharmacological, hemodynamic and autonomic nervous system mechanisms responsible for the blood pressure and heart rate lowering effects of pergolide in rats. J Pharmacol Exp Ther 228:779–791Google Scholar
- Clapham JC, Hamilton TC (1982) Presynaptic dopamine receptors mediate the inhibitory action of dopamine agonists on stimulation-evoked pressor responses in the rat. J Auton Pharmacol 2:181–188Google Scholar
- Dupont AG, Lefebvre RA, Bogaert MG (1985a) Inhibitory effects of apomorphine and pergolide on neurogenic vasoconstriction in the hindquarters of the rat. Naunyn-Schmiedeberg's Arch Pharmacol 329:146–151Google Scholar
- Dupont AG, Lefebvre RA, Bogaert MG (1985b) Inhibition by apomorphine of neurogenic vasoconstriction in the in situ autoperfused rat kidney. Naunyn-Schmiedeberg's Arch Pharmacol 330 (Suppl):R32Google Scholar
- Dupont AG, Lefebvre RA, Bogaert MG (1986) Evidence of presynaptic dopamine receptors in the in situ autoperfused mesenteric artery of the rat. Eur J Clin Invest 16:A19Google Scholar
- Fink GD, Brody MJ (1978) Continuous measurement of renal blood flow changes to renal nerve stimulation and intra-arterial drug administration in the rat. Am J Physiol 234 (2):H219-H222Google Scholar
- Hahn RA (1981) Inhibitory effects of pergolide on peripheral adrenergic neurotransmission in spontaneously hypertensive rats. Life Sci 29:2501–2509Google Scholar
- Jackson EK, Campbell WB (1980) The in situ blood perfused rat mesentery; a model for assessing modulation of noradrenergic neurotransmission. Eur J Pharmacol 66:217–224Google Scholar
- Langer SZ (1980) Presynaptic regulation of the release of catecholamines. Pharmacol Rev 32:337–362Google Scholar
- Lokhandwala MF, Barrett RJ (1982) Cardiovascular dopamine receptors: Physiological, pharmacological and therapeutic implications. J Auton Pharmacol 3:189–215Google Scholar
- Lokhandwala MF, Steenberg ML (1984) Selective activation by LY-141865 and apomorphine of presynaptic dopamine receptors in the rat kidney and influence of stimulation parameters in the action of dopamine. J Pharmacol Exp Ther 228:161–167Google Scholar
- Willems JL, Buylaert WA, Lefebvre RA, Bogaert MG (1985) Neuronal dopamine receptors on autonomic ganglia and sympathetic nerves and dopamine receptors in the gastrointestinal system. Pharmacol Rev 37:165–216Google Scholar