The effects of pH changes on human and ferret detrusor muscle function.

1. The effects of altering extracellular pH on the electrically evoked contractions of ferret and human bladder (detrusor) smooth muscle have been investigated. pH was varied by changing superfusate PCO2 or NaHCO3 concentration. Acidosis increased force when superfusate PCO2 was raised but decreased force when the NaHCO3 concentration was reduced. 2. Intracellular pH (pHi) in isolated ferret detrusor cells was measured separately by epifluorescence microscopy. Extracellular pH changes caused by altering superfusate PCO2 were accompanied by similar changes of pHi, whereas variation of the NaHCO3 concentration had smaller effects on pHi. 3. It was proposed that intracellular acidosis increased contraction but extracellular acidosis depressed contraction. 4. Other interventions, such as addition and removal of NH4Cl, Cl- replacement, and NaHCO3 replacement with HEPES, changed pHi and had predictable effects on force. It was possible to describe unique relationships between tension and either intracellular or extracellular pH regardless of the means whereby pH changes were brought about. 5. Resting tension was reduced whether brought about by either intracellular or extracellular acidosis. K+ contractures were similarly affected by acidosis. Ferret preparations showed low levels of spontaneous activity, which was reduced by acidosis and enhanced by alkalosis.

Renin and angiotensin converting enzyme concentrations in the fetal and neonatal guinea-pig.

1. Plasma renin concentration (PRC) and plasma and pulmonary angiotensin converting enzyme (ACE) concentration were measured in fetal and neonatal guinea-pigs from 45 days gestational age (GA) until 21 days post-partum. 2. Fetal PRC increased towards term to reach values greater than those measured in normal adult males. Pentobarbitone anaesthesia of the mother resulted in significant elevation of fetal PRC after 66 days GA but not before this time. 3. PRC were very high in the newborn guinea-pig, decreased rapidly during the first 24 h after birth and then more gradually, to reach approximately adult values by day 21. 4. Fetal plasma ACE concentration increased towards term to reach values greater than those measured in adult males and decreased subsequently. 5. Pulmonary ACE concentrations were very low throughout gestation but increased considerably between days 3 and 14 post-partum. Low concentrations of ACE were measured in other fetal tissues but placental concentrations were relatively high. 6. Propranolol (0.1 mg I.P.) or saline was administered (under halothane-nitrous oxide anaesthesia) to fetuses of litters of various GA from 55 days to term. Fetal PRC were measured 3 h later. Propranolol treatment resulted in significantly lower fetal PRC than saline treatment in litters aged 63 days to term but not in younger litters. 7. These data indicate that the renin-angiotensin system is functional in the fetal guinea-pig during the last third of gestation. Fetal plasma renin concentrations near term are greater than those measured in normal adult males. This may, in part, reflect an increased influence of the fetal sympathetic nervous system.

Prevention of glucose-induced hypotension by the somatostatin analogue octreotide (SMS 201-995) in chronic autonomic failure: haemodynamic and hormonal changes.

1. The haemodynamic and hormonal changes following glucose ingestion (1 g/kg) were determined before and after pretreatment with either placebo or the somatostatin analogue, octreotide (SMS 201-995, 50 micrograms subcutaneously), in seven patients with chronic autonomic failure. 2. In the placebo phase, after glucose, there was a marked and prolonged fall in blood pressure with no change in cardiac index and peripheral blood flow. Plasma insulin and neurotensin levels increased, whereas glucagon, vasoactive intestinal polypeptide, noradrenaline and adrenaline levels were unchanged. 3. Octreotide transiently raised blood pressure and prevented glucose-induced hypotension. There were no changes in cardiac index or peripheral blood flow. Plasma insulin and neurotensin levels did not rise. Plasma glucose levels increased more slowly but reached a similar level to the placebo phase. 4. We conclude that in autonomic failure patients, glucose-induced hypotension was not accompanied by changes in cardiac index or peripheral blood flow, indicating a lack of compensation to probable splanchnic vasodilatation. The hypotension was prevented by the peptide release inhibitor, octreotide, with no change in cardiac index or in peripheral blood flow, suggesting an effect on the splanchnic vasculature, probably through inhibiting release of vasodilatatory pancreatic and gut peptides.