PubMed Health⌕ Search

Biomedical subjects

C Drummer

Publications and source records attributed to C Drummer.

At least 55 records · Page 3Linked to original sources
PubMed1995

The volume protective natriuretic peptide system in the inner ear. Comparison between vestibular and cochlear compartments.

It has been suggested that the family of natriuretic peptides (NP) has a protective role in volume overloading. Specific binding sites for atrial natriuretic peptide (ANP) and the kidney analog urodilatin (URO) were identified and quantified with computerized autoradiography and biochemical assay in the cryosection in the cochlear and vestibular (utricle/ampulla) tissue. Immunohistochemistry was used to identify and localize NP-like immunoreactive cells. Different levels of specific receptors between and within the inner ear compartments were detected. The presence of specific receptors for NP, as well as unequal distribution of NP-immunoreactivity between the compartments (in certain parts of the cochlea and the endolymphatic sac), may indicate a local autocrine and/or paracrine action of these peptide systems (presumably as a result of the integration of the different peptide effects), independent of their action via the more conventional systemic route, in addition to differences in response of the inner ear compartments to the load. The present results on specific binding of ANP and URO in the inner ear tissue may suggest physiological homology between the inner ear and the kidney. Moreover, a similar role of NP in these organs is suggested.

Atrial Natriuretic Factor↗
PubMed1994

Antinatriuretic kidney response to weightlessness.

We have tested the effects of weightlessness on renal function in one subject who flew the recent week-long Russian-German MIR'92 space mission. Urine flow, renal sodium excretion, and the excretion of urodilatin were measured during the first and last days of the flight. Our results demonstrated, in contrast to expectations, that urine flow and sodium excretion during weightlessness were actually lower than the values obtained during preflight measurements. These results therefore are inconsistent with the commonly held hypothesis that weightlessness induces a diuresis and natriuresis in human subjects. It would seem that further studies are necessary to resolve this issue and to determine whether currently used ground-based models of weightlessness correctly predict physiological adaptations that occur during space flight.

Atrial Natriuretic Factor↗
PubMed1994

Natriuresis in conscious dogs caused by increased carotid [Na+] during angiotensin II and aldosterone blockade.

The renal response to a selective increase in the Na+ concentration of the blood perfusing the central nervous system was investigated in conscious dogs treated with the converting enzyme inhibitor enalaprilat and the aldosterone antagonist canrenoate. In split-infusion experiments the plasma [Na+] of carotid blood was increased (approx. 6 mM) by bilateral infusion of hypertonic NaC1. Concomitantly distilled water was infused into the v. cava making the sum of the infusions isotonic. In control experiments isotonic saline was infused at identical rates into all three catheters. Na+ excretion increased markedly in both series, 103 +/- 14 to 678 +/- 84 mumol min-1 during split-infusion and 90 +2- 14 to 496 +/- 74 mumol min-1 during the isotonic volume expansion. Peak rate of excretion, peak fractional sodium excretion, and cumulative sodium excretion were all significantly higher (P < 0.05) during split-infusion than during control experiments. Plasma vasopressin increased only during split-infusion (0.68 +/- 0.11 to 2.4 +/- 0.8 pg ml-1) while the increases in plasma atrial natriuretic peptide were similar in the two series. Urinary excretion of urodilatin (ANP95-126) increased significantly more during split-infusion (46 +/- 11 to 152 +/- 28 fmol min-1) than during the isotonic volume expansion (45 +/- 14 to 84 +/- 16 fmol min-1) (P < 0.05). It is concluded that the natriuretic mechanisms activated by a selective increase in the Na+ concentration of carotid blood and associated with increased excretion of urodilatin cannot be eliminated by blockade of the renin-angiotensin-aldosterone system.

Angiotensin II↗
PubMed1994

Effect of water temperature on diuresis-natriuresis: AVP, ANP, and urodilatin during immersion in men.

Effects of water temperature on diuresis, natriuresis, and associated endocrine responses during head-out immersion were studied in eight men (23.4 +/- 0.3 yr) during four 5-h experimental conditions: air control at 28 degrees C and immersion at 34.5 degrees C [thermoneutral (Tnt)], 36 degrees C [above Tnt (aTnt)], and 32 degrees C [below Tnt (bTnt)]. Esophageal temperature decreased by approximately 0.4 degrees C in bTnt and increased by approximately 0.5 degrees C in aTnt. Cardiac output increased by approximately 80% in aTnt and approximately 40% in bTnt while thoracic impedance, an index of central blood pooling, decreased by 7.5 omega in bTnt (NS vs. Tnt) and 8.8 omega in aTnt (P < 0.05 vs. Tnt and bTnt). Total peripheral resistance decreased at all temperatures (50% in aTnt, 20% in bTnt). Urine flow and Na+ excretion increased by sixfold in bTnt and Tnt but by only threefold in aTnt. Creatinine clearance was unchanged while osmolal clearance (but not free water clearance) increased two-fold with all immersions. Plasma atrial natriuretic peptide (ANP), urinary urodilatin, and urinary guanosine 3',5'-cyclic monophosphate increased while plasma renin activity, aldosterone, and arginine vasopressin (AVP) decreased similarly at all temperatures. bTnt did not potentiate diuresis by selective attenuation of AVP. The overall natriuretic response exhibited a higher correlation with urodilatin (r = 0.45, P < 0.001) than with ANP (r = 0.26, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Influence of the cGMP analog 8-PCPT-cGMP on agonist-induced increases in cytosolic ionized Ca2+ and on aggregation of human platelets.

The present study was undertaken to compare inhibitory effects of the cGMP analog 8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphate (8-PCPT-cGMP) on increases in cytosolic ionized Ca2+ and on aggregation in human platelets induced via diverse agonists. Fura-2-loaded and gel-filtered platelets were stimulated by either ADP (8 microM), thrombin (0.025 IU/ml) or collagen (1-3 micrograms/ml), respectively. The cGMP analog induced a concentration-dependent inhibition of cytosolic ionized Ca2+ increases and of aggregation to all agonists investigated with half-maximal inhibiting effects of approximately 100 microM. The data obtained suggest that both platelet Ca2+ exchange and aggregation have a similar sensitivity to the cGMP analog. In accordance with previously found significant differences between the potencies of nitric oxide (NO)-generating substances to inhibit increases in cytosolic ionized Ca2+ and aggregation, it appears that the antiplatelet effects of NO-releasing agents could only partially be explained by the elevation of cGMP levels.

Adenosine Diphosphate↗
PubMed1993

Effects of nitric oxide-containing compounds on increases in cytosolic ionized Ca2+ and on aggregation of human platelets.

The present study was undertaken to determine the modulatory effects of nitric oxide (NO)-releasing compounds on increases in cytosolic ionized calcium ([Ca2+]i) and on aggregation of gel-filtered human platelets induced via diverse agonists. We used various sydnonimines and organic nitrates as donors of NO. Gel-filtered and fura-2-loaded platelets were stimulated with ADP (4-8 microM), collagen (2-10 micrograms/ml) or thrombin (0.02-0.05 IU/ml), respectively. Half-maximal inhibiting effects of sydnonimines on agonist-evoked increases in [Ca2+]i were observed between 30 and 1000 nM, while half-maximal inhibiting effects of the compounds on aggregation were between 3 and 500 nM. The compound C 87-3754, which is the bioactive metabolite of pirsidomine, was a much stronger inhibitor of increases in [Ca2+]i than of platelet aggregation. This was due to an enhanced NO release from this compound exposed to ultraviolet light during Ca2+ measurement. The organic nitrates isosorbide 5-mono-nitrate and nicorandil inhibited both aggregation and increase of cytosolic ionized calcium in stimulated platelets at half-maximal concentrations of approximately 200 microM. The present results suggest that some of the effects of NO on platelets are independent of cytosolic ionized calcium. The results also suggest that some of the inhibitory effects of NO-releasing compounds correspond rather to the presence of the A forms (NO-containing intermediates) than to the presence of free NO.

Calcium↗
PubMed1993

Reduced natriuresis during weightlessness.

The kidney response to weightlessness was measured in one volunteer during a 1-week space mission. Shortly after entering microgravity and later during the mission, consecutive urine sampling periods were monitored, covering in total about 50% of the inflight time. Preflight references were a sequence of ground-based experiments, which evaluated body fluid metabolism with different degrees of standardization. Additional variables, such as circadian rhythms and cortisol-associated stress, were also monitored. In contrast to current hypotheses, the volunteer showed a pronounced reduction in natriuresis and diuresis during the entire space flight, despite a considerable weight loss. For the first time, the urinary excretion of the renal natriuretic peptide urodilatin was also measured. Both, during the preflight experiments and during weightlessness, close correlations between urodilatin excretion and sodium excretion were observed. However, the correlation between natriuresis and urodilatin excretion was considerably altered during weightlessness. We conclude that the loss of body weight during space flight is not related to an increased renal fluid loss and that urodilatin might counteract the decrease in renal excretion observed in weightlessness.

Atrial Natriuretic Factor↗
PubMed1993

Long-term elevations of dietary sodium produce parallel increases in the renal excretion of urodilatin and sodium.

The effects of dietary sodium intake on the renal excretion of urodilatin and of sodium were examined in six healthy male subjects. The 24-day study period was divided into three phases of 8 days each. Subjects ingested 2.8 mequiv sodium (kg body weight)-1 day-1 during the first phase, 5.6 mequiv (kg body weight)-1 day-1 during the second phase, and 8.4 mequiv (kg body weight)-1 day-1 during the third phase. The excretion of both sodium (P < 0.002) and urodilatin (P < 0.006) increased in response to the increasing dietary sodium, while urine flow did not change. Urinary urodilatin excretion correlated closely with renal sodium excretion (P < 0.001). Serum aldosterone levels (P < 0.01) as well as serum renin levels (P < 0.05) significantly decreased with increasing sodium intake. Plasma [Arg]vasopressin levels increased significantly (P < 0.05). Plasma atrial natriuretic factor and cGMP levels as well as urinary cGMP excretion rates were unaltered by the changes in sodium intake. We conclude from these results that the renal natriuretic peptide, urodilatin, but not the main cardiac member of the natriuretic peptide family may be involved in the regulation of day-to-day sodium balance.

Adult↗
PubMed1993

Development and application of a urodilatin (CDD/ANP-95-126)-specific radioimmunoassay.

Urodilatin, a renal natriuretic peptide that is an analogue to circulating atrial natriuretic peptide [alpha-ANP(99-126)], is measurable with a highly specific and sensitive radioimmunoassay. While most ANP antibodies cannot distinguish between urodilatin and other ANP analogues, the polyclonal urodilatin antibody specifically measures human urodilatin without any cross-reactivity to other ANP analogues. Urodilatin is not detected in blood from healthy volunteers nor from cardiac patients. Urinary urodilatin accounts for only a part of total urinary ANP immunoreactivity. Urodilatin excretion closely parallels sodium excretion in response to an acute volume load while changes in urinary immunoreactive ANP excretion do not reflect this renal response. We conclude that specific urodilatin assays are required to explore further the physiological role of the renal natriuretic peptide.

Amino Acid Sequence↗
PubMed1993

Is the renal natriuretic peptide urodilatin involved in the regulation of natriuresis?

Recent evidence has shown that the kidneys produce and secrete a member of the atrial natriuretic peptide family, named urodilatin. This 32-amino acid peptide does not circulate in blood, but is secreted into urine. Urodilatin excretion closely parallels renal sodium excretion under various conditions that influence body fluid regulation, such as circadian rhythm, salt ingestion, acute intravenous sodium loading, water immersion, atrial distension, and cerebral hypernatremia. In contrast, the plasma concentration of the atrial member of the natriuretic peptide family often is only weakly and occasionally even negatively associated with natriuresis under these conditions. We conclude from these observations that urodilatin rather than atrial natriuretic peptide might be the member of the natriuretic peptide family that is involved in the regulation of natriuresis in normal physiology.

Animals↗
PubMed1993

Effect of water immersion on renal natriuretic peptide (urodilatin) excretion in humans.

We examined 1) the effect of thermoneutral (34.5 +/- 0.5 degrees C) water immersion to the neck (WI) in humans on the temporal profile of renal urodilatin [atrial natriuretic peptide- (ANP) (95-126)] excretion and 2) the relationship between urodilatin and urinary fluid (V) and sodium (UNaV) excretion. Eight normal subjects underwent 12 h of WI, and another group of eight were studied during seated control conditions. The subjects ingested 200 ml of tap water hourly. WI induced an increase in renal urodilatin and guanosine 3',5'-cyclic monophosphate (cGMP) excretion, V, and UNaV. After peak values were attained between the 2nd and 5th h of WI, urodilatin and cGMP excretion, V, and UNaV returned toward preimmersion and control levels. At the 12th h of WI, urodilatin and cGMP excretion and V were indistinguishable from preimmersion values but were significantly elevated compared with the control values. UNaV was maintained elevated compared with both preimmersion and control values. During WI, positive and statistically significant linear correlations could be established between V and renal urodilatin excretion in six subjects and between UNaV and urodilatin excretion in four subjects. We conclude that WI induces an increase in the rate of renal urodilatin excretion, attaining a peak value at the 3rd h followed by an attenuation toward preimmersion and control levels. Furthermore, urodilatin might participate as one of several mechanisms of the natriuresis and diuresis of WI in humans.

Adult↗
PubMed1993

Plasma cGMP level as a marker of the hydration state in renal replacement therapy.

We investigated, whether plasma cyclic guanosine 3':5'-monophosphate (cGMP) may be suited as a marker of hyperhydration in hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD). In 81 HD patients the levels of atrial natriuretic peptide (ANP) and cGMP were markedly elevated before HD (ANP: 165 +/- 11.1 pg/ml; cGMP 43.5 +/- 2.2 pmol/ml). Significantly lower values (P < 0.01) were found after HD (ANP: 97 +/- 8.4 pmol/ml; cGMP 19.5 +/- 1.5 pmol/ml). Twenty-three patients had cGMP levels above 20 pmol/ml after HD. Therefore "dry body weight" was reduced in these patients. This resulted in a "normalization" of cGMP values to a postdialytic range below 20 pmol/ml in the majority of patients. All seven patients with persistently high cGMP levels despite weight reduction had left sided heart failure. In 33 CAPD patients ANP was slightly lower than after HD (68 +/- 10.4 pg/ml), and the cGMP level (22.4 +/- 2.3 pmol/ml) was between pre- and postdialytic values in HD. In eight CAPD patients with clinical signs of hypervolemia plasma cGMP, but not ANP, was significantly elevated. We conclude that the plasma cGMP level appears to be a reliable marker for fluid overload in patients on renal replacement therapy with normal heart function.

Adult↗
PubMed1992

Haemodynamic and renal effects of urodilatin bolus injections in patients with congestive heart failure.

Urodilatin (ANF(95-126)) is an analogue of the atrial natriuretic factor (ANF(99-126)), which has been isolated from human urine. Recently we have shown in healthy volunteers, that intravenous bolus injections of synthetic urodilatin produce more pronounced reductions of pulmonary arterial pressure than ANF(99-126). To compare haemodynamic and renal effects of synthetic urodilatin with those of ANF(99-126) in congestive heart failure (CHF), 12 patients (66.3 +/- 1.4 years) received either two high dose intravenous bolus injections of 4 micrograms kg-1 bw Urodilatin (URO) at a 30 min interval (n = 6) or the same doses of ANF(99-126) (n = 6). Prior to i.v. URO, no URO immunoreactivity was found in human plasma (specific RIA, no crossreactivity to ANF). Similar to ANF, the increase in diuresis (1.4 +/- 0.7 to 3.7 +/- 1.6 ml min-1) and natriuresis (169 +/- 114 to 430 +/- 197 mumol min-1) was moderate after URO in CHF. During the 90 min study period, mean plasma cyclic GMP levels increased much more after URO (by 53.4 +/- 15.1 nM) than after ANF (by 13.1 +/- 3.0 nM; P = 0.04). In contrast to ANF, i.v. bolus injections of URO produced sustained haemodynamic effects in CHF lasting up to 90 min: The average (0-90 min) reduction of systemic vascular resistance was more pronounced after URO (-578 +/- 148) than after ANF (-204 +/- 65 dyn*s*cm-5, P = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Haemodynamic and renal effects of urodilatin in healthy volunteers.

Urodilatin (ANF(95-126)), an analogue of the atrial natriuretic factor (ANF(99-126)), has recently been isolated from human urine. To study haemodynamic and renal effects of synthetic urodilatin, 18 healthy male volunteers (age 26.1 +/- 0.8 years; X +/- SEM) received i.v. bolus injections of urodilatin at doses of 1, 2 or 4 micrograms kg-1 body weight (bw) (n = 6 per dosage group). Urodilatin dose-dependently increased heart rate and cardiac index. A dose-dependent increase in plasma cyclic GMP levels was also observed. Urinary cyclic GMP excretion, urine flow and natriuresis increased 7-fold, 5-fold and 4-fold, respectively. Renal effects were not different between dosage groups. Compared with ANF(99-126), after urodilatin the reduction in mean pulmonary arterial pressure (PAP) was more pronounced (2 micrograms kg-1, n = 6; ANF -1.8 +/- 0.5, URO: -5.5 +/- 1.1 mmHg, P less than 0.05). Furthermore, after urodilatin the reduction of PAP lasted continuously from 2 up to 90 min after injection, while ANF(99-126) produced only a transient decrease of PAP. Similarly the reduction of pulmonary capillary wedge pressure (PCWP) by urodilatin from 9.3 +/- 1.2 to 3.8 +/- 0.9 mmHg (P less than 0.05) was also sustained up to 90 min post administration. These data in healthy volunteers suggest that, due to prolonged reduction of PAP and PCWP with increases of cardiac index and reduction of systemic vascular resistance, urodilatin might exhibit beneficial effects in cardiovascular disease.

Adult↗
PubMed1992

Roles of cephalic Na+ concentration and urodilatin in control of renal Na+ excretion.

Effects on renal function of an increase in the concentration of sodium in the blood supplying the head were investigated in water-diuretic conscious dogs in which the sodium and water contents were controlled by separate servo-mechanisms. A selective 2% increase in the sodium concentration of the carotid blood was achieved by a split-infusion technique including infusions of hypertonic saline into both carotid arteries and water into a jugular vein at rates making the combined infusate isotonic. This procedure caused a 34-fold increase in renal sodium excretion concomitant with a fourfold increase in the rate of urinary excretion of urodilatin. A comparable isotonic volume expansion (isotonic saline infusion into carotid arteries and jugular vein) caused a significantly smaller (13-fold) increase in urinary rate of excretion of sodium (P less than 0.02) and no increase at all in the excretion of urodilatin. It is hypothesized that cephalic sodium concentration receptors regulate the rate of excretion of sodium via urodilatin even under the present slightly hypotonic conditions.

Animals↗