Renal effects of adrenomedullin in the rat.

We investigated the effects of a constant infusion of adrenomedullin (ADM) on renal hemodynamics and fluid electrolyte excretion in the rat. Following baseline measurements, eight rats received an intravenous infusion of 5 micrograms of rat ADM (167 ng/min) for 30 min at 10 microliters/min. Eight additional rats received 0.9% saline at 10 microliters/min instead of ADM. Renal function was measured during this period and for two consecutive 20-min periods following termination of the ADM or vehicle infusion. Mean arterial pressure decreased from a baseline of 113 +/- 3 to 102 +/- 1 mm Hg at 25 min of ADM infusion and returned towards control after the ADM infusion was terminated. This modest hypotensive effect was associated with an increase in heart rate from 366 +/- 10 to 384 +/- 9 bpm, which continued to remain elevated after the ADM infusion was stopped. Urinary sodium excretion increased from 348 +/- 57 to 813 +/- 172 nEq/min during ADM infusion and continued to increase to 1141 +/- 347 nEq/min after the infusion of ADM was terminated. Urinary potassium excretion increased from 1.94 +/- 0.22 to 2.75 +/- 0.24 microEq/min during ADM infusion. Urine flow tended to increase (P = 0.08) from 7.0 +/- 0.5 to 8.1 +/- 0.6 microliters/min during ADM infusion and continued to increase to 9.7 +/- 1.5 microliters/min after the infusion was stopped. Renal plasma flow increased from 3.22 +/- 0.22 to 3.82 +/- 0.20 ml/min/g kidney wt during ADM infusion and continued to increase to 4.14 +/- 0.22 ml/min/g kidney wt after the ADM infusion was stopped. Glomerular filtration rate averaged to 1.11 +/- 0.07 ml/min/g kidney wt during baseline and did not significantly change during or after ADM infusion. These results indicate that a constant infusion of adrenomedullin, at a dose that results in a minimal hypotensive effect increases renal plasma flow and urinary sodium excretion in the rat.

Differential influence of electrical blocking agents on embryonic acetylcholine receptor mRNA levels in long-term cultures of aneural mammalian myotubes.

The influence of spontaneous muscle activity on acetylcholine receptor (AChR) expression was examined by exposing long-term cultures of mammalian myotubes to two pharmacological agents that have similar effects on the rate of spontaneous contractile activity but pharmacologically distinct actions on voltage gated Na+ channels. Previous studies by other investigators have shown that tetrodotoxin upregulates and that veratridine downregulates surface AChR expression in short-term mammalian muscle cultures. In order to determine whether these drugs have disparate actions on AChR mRNA levels, myotubes were exposed to either tetrodotoxin or veratridine for a period of 10 days, and measurements of the relative levels of embryonic AChR subunit mRNAs (alpha, beta, gamma, delta) were obtained during and following the period of drug exposure. Veratridine produced a substantial decrease (between 33% and 50% reduction), while tetrodotoxin produced a relatively small increase (between 17% and 23%), in each of the AChR subunit mRNAs after 6 days of drug exposure. At 23 days in culture, spontaneously active myotubes exhibited a decrease in the relative levels of each of the AChR subunit mRNAs. Myotubes previously exposed to either veratridine or tetrodotoxin exhibited elevated levels of beta, gamma, and delta AChR subunit mRNAs 6 days after cessation of drug treatment, thus suggesting that a period of muscle inactivity can induce sustained influences on some AChR mRNA levels.(ABSTRACT TRUNCATED AT 250 WORDS)