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Am J Physiol. 1986 Jun;250(6 Pt 2):F999-1007.
Interaction between epinephrine and renal nerves in control of renin secretion rate.

Kopp UC, DiBona GF.

To determine whether the increase in renin secretion rate (RSR) produced by the beta 2-adrenoceptor agonist epinephrine was dependent on intact renal innervation, epinephrine (10 ng X kg-1 X min-1) was infused bilaterally into an innervated and a denervated kidney (ira) of the same anesthetized dog at spontaneous and reduced renal arterial pressure (decreases RAP, 100 mmHg). Epinephrine ira did not affect mean arterial pressure, renal hemodynamics, or urinary sodium excretion of either kidney. At spontaneous RAP epinephrine ira increased RSR from 633 +/- 134 to 926 +/- 137 ng/min in innervated kidneys but did not change RSR in denervated kidneys. decreases RAP in the presence of epinephrine ira resulted in an increase in RSR from 969 +/- 248 to 2,564 +/- 630 ng/min in innervated kidneys, which was greater than that produced in the absence of epinephrine, from 741 +/- 244 to 1,606 +/- 431 ng/min. In denervated kidneys decreases RAP resulted in similar increases in RSR in the absence and presence of epinephrine ira from 41 +/- 15 to 166 +/- 60 ng/min and from 59 +/- 210 to 235 +/- 78 ng/min, respectively. These results demonstrate that the increase in RSR produced by epinephrine is dependent on intact renal innervation at spontaneous and decreases RAP and suggest that epinephrine increases RSR by a prejunctional mechanism. The beta 1-adrenoceptor antagonist metoprolol (0.3-0.5 microgram X kg-1 X min-1 ira) abolished the enhanced RSR response to decreases RAP produced by epinephrine ira. Similarly, the beta 2-adrenoceptor antagonist ICI 118551 (0.005-0.25 microgram X kg-1 X min-1 ira) abolished the enhanced RSR response to decreases RAP produced by epinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)

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Microvasc Res. 1990 Jan;39(1):50-9.
Demonstration of both beta 1- and beta 2-adrenoceptors mediating negative chronotropic effects on spontaneous activity in isolated bovine mesenteric lymphatics.

Watanabe N, Kawai Y, Ohhashi T.

First Department of Physiology, Shinshu University School of Medicine, Matsumoto, Japan.

The pharmacological classification of beta-adrenoceptor subtypes in isolated bovine mesenteric lymphatics was studied by using various beta-adrenoceptor agonists and antagonists. Isoproterenol (ISP) (10(-10)-10(-8) M) produced dose-dependent negative chronotropic effects on the rhythm of spontaneous contractions in the lymphatic preparation. The ISP-induced effects were dose-dependently blocked by pretreatment with 10(-8)-10(-7) M metoprolol (a selective beta 1 antagonist) as well as 10(-8)-10(-7) M propranolol (a beta 1 and beta 2 antagonist). Dobutamine (a selective beta 1 agonist) caused a dose-dependent negative chronotropic effect, which was significantly blocked by pretreatment with 10(-8) M metoprolol. Salbutamol and procaterol (selective beta 2 agonists) also produced dose-dependent negative chronotropic effects, which were dose-dependently inhibited by pretreatment with 10(-8)-10(-7) M propranolol, but not by 10(-7) M metoprolol. The decreasing order of the relative potency was as follows: ISP greater than procaterol greater than salbutamol greater than dobutamine. These results suggest that bovine mesenteric lymphatics contain both beta 1- and beta 2-adrenoceptors and that both subtypes can produce a negative chronotropic effect on the rhythm of spontaneous contractions, when stimulated.

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cc.kangwon.ac.kr

Achiral chiral column switching HPLC assay was developed to allow the separation and quantitation of the enantiomers of metoprolol in human urine by means of fluorescence detection. Urine samples were prepared by liquid liquid extraction, followed by HPLC. The racemic metoprolol and internal standard were separated from the interfering components in urine and quantified on the silica column, and the enantiomers were determined on a Chiralcel OD chiral stationary phase. The two columns were connected by a switching valve equipped with a silica trap column. Detection limit was 25 ng/ml for each enantiomer. The intra-day variation ranged between 0.38 and 4.94% in relation to the measured concentration and the inter-day variation was 0.15-3.13%. It has been applied to the determination of (R)-(+)-metoprolol and (S)-(-)-metoprolol in urine from healthy volunteers dosed with racemic metoprolol tartrate.

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