Biomedical subjects

C T Stier

Publications and source records attributed to C T Stier.

At least 37 records · Page 2Linked to original sources

PubMed1992

Endothelin-3 effects on renal function and prostanoid release in the rat isolated kidney.

The direct effects of rat endothelin (ET-3) on renal function and prostanoid levels were examined in the isolated, oncotically perfused kidney of the rat. ET-3 at 0.75 and 2.0 ng/ml produced sustained increases in perfusion pressure of 46 and 83 mm Hg, respectively, as compared with control kidneys. Glomerular filtration rate was significantly higher than control after additions of ET-3 as was the absolute and fractional excretion of water and electrolytes. ET-3 increased perfusate 6-keto-prostaglandin (PG)F1 alpha (breakdown product of PGI2) levels and stimulated greater urinary excretion of PGE2 and PGF2 alpha than 6-keto-PGF1 alpha. ET-3 did not affect urinary excretion or perfusate levels of thromboxane B2. Time-dependent increases in renin release were suppressed by ET-3. Indomethacin (10 microM) prevented ET-3-induced increases in urinary and perfusate prostanoids; however, renal vasoconstrictor and excretory responses were the same in the presence or absence of indomethacin. These results indicate that ET-3 acts directly on the perfused rat kidney to increase the release of prostanoids from the vascular and urinary compartments. A modulatory influence of prostaglandins on the acute renal hemodynamic and excretory effects of ET-3 was not observed under these conditions.

Animals↗

PubMed1991

Dietary arginine fails to protect against cerebrovascular damage in stroke-prone hypertensive rats.

Stroke-prone spontaneously hypertensive rats (SHRSP) develop severe hypertension and cerebrovascular lesions. We investigated the influence of dietary supplementation with L-arginine, an amino acid precursor of endothelium-derived nitric oxide, on blood pressure and stroke in these rats. L-Arginine, administered in the saline drinking solution at 2 or 6 g/l starting at 8.7 weeks of age, was without effect on blood pressure, cerebrovascular lesions, or longevity despite continuous treatment through 14 weeks of age. These findings do not support a beneficial influence of dietary arginine in the cerebrovascular pathology of SHRSP.

Animals↗

PubMed1991

Therapeutic benefit of captopril in salt-loaded stroke-prone spontaneously hypertensive rats is independent of hypotensive effect.

In the present study we examined whether the angiotensin I converting enzyme inhibitor, captopril, would protect stroke-prone spontaneously hypertensive rats (SHRSP) from stroke and renal pathology over a 26-week period. In the control group of six untreated SHRSP fed Stroke-Prone Rodent Diet and 1% NaCl drinking solution, all animals developed severe hypertension and stroke by 16.1 weeks of age. In eight salt-loaded SHRSP treated with oral captopril (50 mg/kg/day) beginning at 8.4 weeks of age, systolic blood pressure was slightly but temporarily suppressed and then continued to rise; by 12 weeks of age systolic blood pressure reached levels of severe hypertension, 240 +/- 8 mm Hg, and did not differ from that of untreated SHRSP. No deaths or brain lesions were noted in captopril-treated SHRSP despite severe hypertension maintained through 26 weeks of age when the study ended. Captopril treatment prevented increases in urinary protein excretion (14 +/- 2 v 63 +/- 16 mg/day at 11.7 weeks of age, P less than .01) and the severe brain, renal, and cardiac vascular lesions observed in untreated SHRSP. When maintained on Stroke-Prone Rodent Diet and saline, plasma renin activity of untreated SHRSP surviving until 14.5 weeks of age was markedly increased (29.1 +/- 9.4 ng Ang I/mL/h) compared with either untreated SHRSP (9.2 +/- 2.5 ng Ang I/mL/h, P less than .01) or Wistar-Kyoto rats (3.5 +/- 1.0 ng Ang I/mL/h, P less than .01) maintained on standard diet and water.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1991

Role of prostanoids in renin-dependent and renin-independent hypertension.

We investigated the role of prostanoid-mediated pressor mechanisms in setting the level of blood pressure in renin-dependent and renin-independent models of hypertension in unanesthetized rats. Intravenous administration of a blocker of thromboxane A2/prostaglandin endoperoxide receptors, SQ29548 (2 mg/kg bolus injection plus 2 mg/kg/hr for 3 hours), reduced from 162 +/- 4 to 144 +/- 5 mm Hg (p less than 0.05) the blood pressure of rats with aortic coarctation-induced hypertension at 7-14 days after coarctation when plasma renin activity is greatly increased. In contrast, treatment with SQ29548 was without effect on the blood pressure of either normotensive or hypertensive rats (i.e., aortic coarctation-induced hypertension at 90-113 days after coarctation, deoxycorticosterone-salt-induced hypertension) having normal or depressed values of plasma renin activity. The blood pressure-lowering effect of SQ29548 in the early phase of aortic coarctation-induced hypertension was positively correlated with the prevailing plasma renin activity and could not be demonstrated in hypertensive rats pretreated with indomethacin. We attribute the hypotensive effect of SQ29548 to interference with pressor mechanisms that depend on activation of thromboxane A2/prostaglandin endoperoxide receptors and suggest that such prostanoid-mediated mechanisms are operational and contribute to an increase in blood pressure in angiotensin-dependent forms of hypertension. Also prostanoid-mediated vasodepressor mechanisms are operational in the early phase of aortic coarctation-induced hypertension since the blood pressure of rats pretreated with SQ29548 was increased by the subsequent administration of indomethacin. Accordingly, the blood pressure of rats with aortic coarctation-induced hypertension is influenced by the interplay of prostanoid-mediated pressor and vasodepressor mechanisms.

6-Ketoprostaglandin F1 alpha↗

PubMed1989

Serotonin and 5-hydroxytryptophan on blood pressure and renal blood flow in anesthetized rats.

The effects of exogenous (injected) serotonin on mean blood pressure and renal blood flow in male Sprague-Dawley rats were compared with the effects of enhanced endogenous serotonin, accomplished by injections of 5-hydroxytryptophan (5-HTP). Responses were evaluated with and without carbidopa, which blocks peripheral conversion of 5-HTP to serotonin, and with and without indomethacin to assess the contribution of prostanoids. Both serotonin (0.25-1.0 micrograms) and 5-HTP (50-200 micrograms) decreased blood pressure and renal blood flow and increased renal vascular resistance in dose-dependent fashion. Hypotensive responses with both agents were greater after arterial injections into the aortic arch than after intravenous injections (into the jugular vein). Carbidopa had no significant effects on responses to serotonin but ablated the ability of 5-HTP to increase renal vascular resistance and decrease renal blood flow. Carbidopa did not alter the hypotensive action of 5-HTP. Indomethacin had no significant effect on responses to serotonin or 5-HTP. These results support a direct renal vasoconstrictor effect for exogenous and endogenously formed serotonin and a hypotensive effect probably arising in the central nervous system.

5-Hydroxytryptophan↗

PubMed1989

Enalapril prevents stroke and kidney dysfunction in salt-loaded stroke-prone spontaneously hypertensive rats.

The influence of chronic treatment with the angiotensin I converting enzyme (ACE) inhibitor enalapril on blood pressure, kidney function, and survival was examined in stroke-prone spontaneously hypertensive rats (SHRSP). Male SHRSP that were fed a Japanese rat chow plus a 1% NaCl drinking solution beginning at 7-8 weeks of age developed severe hypertension and stroke; 14 of 18 untreated control SHRSP died by 14 weeks of age and exhibited evidence of cerebrovascular lesions. When enalapril (15 mg/kg/day) was included in the drinking solution of 15 SHRSP, blood pressure was initially reduced by only a slight degree, whereas survival improved markedly; only one of 10 SHRSP died before the rest were killed at 18 to 21 weeks. The remaining five enalapril-treated SHRSP lived beyond 36 weeks and on histological examination exhibited no evidence of cerebrovascular lesions. Chronic enalapril treatment also prevented the greater urinary excretion of protein and severe renal lesions observed in untreated SHRSP but did not affect urinary salt and water excretion. In anesthetized rats, glomerular filtration rate and tubular reabsorption of water were lower in untreated control SHRSP when compared with enalapril-treated SHRSP. Mean arterial pressure was comparable in both groups. These data support a possible role for ACE inhibition in the prevention of stroke and maintenance of kidney function independent of any marked change in blood pressure of SHRSP. Whether the protective effects of ACE inhibition relate to reduced angiotensin II formation, increased tissue kinins, or another mechanism remains to be determined.

Angiotensin II↗

PubMed1989

5-Hydroxytryptophan and carbidopa in spontaneously hypertensive rats.

Serial measurements of blood pressure, body weight, food and water intake, and salt and water excretion were compared in two groups of spontaneously hypertensive rats (SHR) over a 12-day period: control SHR (n = 11) and a group (n = 9) which received supplementary 5-hydroxytryptophan (5-HTP; 2 mg/ml) in its drinking water. During the final 4 days of study, both groups received additional oral carbidopa (50 mg/kg twice a day) to inhibit peripheral, but not brain aromatic L-amino-acid decarboxylase (LAAD), an enzyme necessary to the formation of 5-hydroxytryptamine (5-HT, serotonin) from 5-HTP. 5-Hydroxytryptophan increased urinary 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) markedly; following carbidopa, urinary 5-HT, and to a lesser degree urinary 5-HIAA, decreased, whereas brain 5-HT and 5-HIAA increased. Spontaneously hypertensive rats treated with 5-HTP plus carbidopa had significantly lower blood pressure levels, lower pulse rates, reductions in food and water intake, salt and water excretion, and a loss of body weight, when compared with the control SHR. These data indicate that enhanced brain formation of 5-HT can give rise to metabolic and circulatory responses with a resultant lowering of blood pressure.

5-Hydroxytryptophan↗

PubMed1988

Thromboxane A2 and the development of hypertension in spontaneously hypertensive rats.

Osmotic minipumps containing OKY-046 (15-20 mg/kg per day), to inhibit thromboxane (TX) A2 synthase, were implanted into 43-day-old SHR and age-matched Wistar-Kyoto rats (WKY) to study the role of TXA2 in the development of hypertension in SHR. Inhibition of TXA2 synthase with OKY-046 did not affect urine volume, sodium excretion, potassium excretion, food and water intake or body weight in either WKY or SHR during the two weeks of study. In the first week systolic blood pressure (SBP) was significantly lower in SHR receiving OKY-046 in comparison to SHR which received no OKY-046 (127 +/- 3 vs. 110 +/- 4 mm Hg, P less than 0.01). OKY-046 did not affect SBP in WKY. By the second week SBP in SHR and WKY receiving OKY-046 did not differ from their respective controls despite an 85% reduction in serum immunoreactive TXB2 (iTXB2; the stable hydrolysis product of TXA2) and a 45% reduction in urinary iTXB2 excretion. These results support a possible role for TXA2 in the developmental stage of hypertension in SHR and other factors in the sustained elevation of blood pressure.

6-Ketoprostaglandin F1 alpha↗

PubMed1988

Reciprocal renal effects of dopamine and 5-hydroxytryptamine formed within the rat kidney.

1. Clearance of inulin and p-aminohippurate and excretion of water and sodium were measured for eight to 11 clearance periods of 20 min duration in anaesthetized, 3% volume-expanded rats, before and after intravenous infusions of the amino acids L-dopa (L-3,4-dihydroxyphenylalanine) and 5-hydroxytryptophan. During the final two clearance periods, the peripheral decarboxylase inhibitor, carbidopa (S-alpha-hydrazino-3,4-dihydroxy-alpha-methylbenzenepropanoic acid monohydrate), was infused additionally. 2. Renal formation of dopamine (3,4-dihydroxyphenethylamine) and 5-hydroxytryptamine was demonstrated during infusions of L-dopa and 5-hydroxytryptophan, respectively; carbidopa blocked the renal formation of these biogenic amines. 3. During infusion of dopa, a diuresis and a natriuresis were observed; during the infusion of 5-hydroxytryptophan, slight reductions in clearances of inulin and p-aminohippurate, but significant reductions in sodium and water excretion, were measured. 4. The addition of carbidopa diminished diuretic and natriuretic responses to dopa as renal dopamine excretion decreased; the infusion of carbidopa also ameliorated the antinatriuretic and antidiuretic effects of 5-hydroxytryptophan, as 5-hydroxytryptamine excretion decreased. 5. Although dopa and 5-hydroxytryptophan are substrates for the same enzyme, aromatic L-amino-acid decarboxylase, simultaneous infusions of both amino acids at comparable rates gave no evidence of competitive inhibition of amine synthesis. However, the infusion of dopa, after 5-hydroxytryptophan, decreased its antinatriuretic and antidiuretic effects. 6. These data raise the possibility that dopamine and 5-hydroxytryptamine are formed as reciprocal intrarenal hormones by the identical enzyme, aromatic L-amino-acid decarboxylase, which is located within cells of the renal tubule.

5-Hydroxytryptophan↗

PubMed1988

Thromboxane A2 in severe hypertension and stroke in stroke-prone spontaneously hypertensive rats.

Thromboxane A2 is a prostanoid having potent platelet aggregatory and vasoconstrictor properties. To determine a possible role for thromboxane A2 in the development of severe hypertension and stroke, we chronically administered the selective thromboxane A2 synthase inhibitor UK-38,485 (Dazmegrel) to stroke-prone spontaneously hypertensive rats (SHRSP). Serum thromboxane B2 (the stable hydrolysis product of thromboxane A2) generation was significantly greater in incubates of whole blood from SHRSP than in those from normotensive control Wistar-Kyoto rats and was inhibited greater than 89% by UK-38,485 administered in vivo. In 10 male SHRSP fed a Japanese-style rat chow and given 1% NaCl in drinking water to accelerate the occurrence of stroke, treatment with 100 mg/kg/day UK-38,485 by gavage starting at 8.6 weeks of age diminished systolic blood pressure elevation at 10 (205 +/- 2 vs. 220 +/- 4 mm Hg, p less than 0.01) and 11 weeks of age (210 +/- 4 vs. 239 +/- 7 mm Hg, p less than 0.01) compared with 10 untreated SHRSP. The ultimate establishment of severe hypertension was not prevented by UK-38,485. Stroke-related mortality was 70% in both UK-38,485-treated and control SHRSP at 14 weeks of age. Histologic examination revealed cerebrovascular lesions consistent with the occurrence of stroke in both control and UK-38,485-treated SHRSP. Our results support a possible role for thromboxane A2 in the elevation of blood pressure in SHRSP but do not support a possible role for the prevention of stroke by thromboxane A2 synthase inhibition in these rats.

Animals↗

PubMed1987

Renal response to 9 alpha, 11 beta-prostaglandin F2 in the rat.

9 alpha, 11 beta-Prostaglandin F2 (9 alpha, 11 beta-PGF2) is a novel PG formed from PGD2 by the action of 11-ketoreductase which has been shown to exist in the liver, lung and kidneys. 9 alpha, 11 beta-PGF2 has been reported to possess platelet antiaggregatory, vasoconstrictor and bronchoconstrictor properties. To define further the biological activity of 9 alpha, 11 beta-PGF2, with respect to kidney function, studies were conducted in anesthetized male Sprague-Dawley rats prepared for renal clearance measurements. Intravenous infusion of highly-purified 9 alpha, 11 beta-PGF2 (2.5 micrograms/min, n = 9) elevated urine flow (28 +/- 6 microliter/min, P less than .05), urinary sodium/potassium (0.96 +/- 0.31, P less than .05), hematocrit (0.5 +/- 0.3, volumes/100 ml, P less than .05) and urinary sodium excretion (2.3 +/- 1.0 microEq/min). Similar responses but of greater magnitude were obtained with PGF2 alpha (2.5 micrograms/min). Glomerular filtration rate (GFR) and mean arterial pressure (MAP) were unaffected. In contrast, PGD2 (2.5 micrograms/min) resulted in decreases in MAP and concomitant reductions in GFR, urine flow and sodium excretion. Abrupt and pronounced increases in urine flow and sodium excretion were observed on administration of 9 alpha, 11 beta-PGF2 at 7.5 micrograms/min. 9 alpha, 11 beta-PGF2 (2.5 micrograms/min) produced consistent increases in urine flow and the excretion of sodium and chloride in rats treated with meclofenamate, 2 mg/kg/hr i.v., indicating that these responses were not dependent on endogenous PG synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Formation of biogenic amines by isolated kidneys of spontaneously hypertensive rats.

Kidneys form dopamine (DA) from L-dopa and serotonin from L-5-hydroxytryptophan (L-5-HTP) via aromatic L-amino acid decarboxylase. We compared the ability of isolated perfused kidneys from adult (20-week-old) spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) to form these biogenic amines. Renal vascular resistance (RVR) was greater in perfused kidneys from SHR (n = 10) than WKY (n = 8) (p less than 0.01). Slight decreases in RVR were observed during L-dopa infusion but these were unrelated to DA formation. L-Dopa infusion was associated with greater DA output in SHR than WKY in both the renal venous and urinary effluents although the latter did not achieve statistical significance. L-5-HTP increased RVR to a greater degree in SHR than WKY kidneys. This was associated with larger quantities of serotonin in the urinary and venous effluents and greater pressor responses to exogenous serotonin in SHR than WKY kidneys; however, either parameter alone was not significantly increased. Our findings do not support a deficiency of intrarenal DA formation as a pathogenic factor for hypertension in SHR. Biogenic amine formation is as great if not greater in SHR than WKY kidneys and appears to contribute largely to the greater increases in renal resistance seen in SHR kidneys on infusion of L-5-HTP. Enhanced renal serotonin formation may elevate blood pressure, whereas enhanced renal DA formation would favor blood pressure lowering, perhaps as a compensatory mechanism.

5-Hydroxytryptophan↗

PubMed1986

Renal calcium metabolism and diuretics.

Diuretic agents have variable effects on calcium excretion as studied in vivo and in isolated kidneys and nephron segments. Generally, by increasing sodium and water excretion, diuretics will cause a concomitant increase in calcium excretion. As they diminish blood volume and alter renal hemodynamics, diuretics enhance calcium reabsorption in the proximal tubule, modulating their usual effects on calcium excretion. These general effects can be further modulated by additional metabolic actions. For instance, chronic administration of thiazide diuretics may diminish calcium excretion on the basis of altered levels of or responsiveness to PTH. Agents such as acetazolamide, which diminish bicarbonate reabsorption in the proximal tubule, will cause a modest calciuria, if any, because of reabsorption of the increased delivery of calcium, but not sodium, at the distal nephron. Agents acting in the loop of Henle that increase chloride excretion relative to sodium tend to cause greater calcium excretion. Finally, agents that act beyond the loop of Henle, which have their primary effects on cation excretion, tend to cause lesser degrees of calcium excretion, especially relative to sodium. These principles indicate that it may be appropriate to select a specific diuretic agent for different patients, depending upon the state of their calcium balance. It also may be possible to predict alterations in calcium balance, so that these may be anticipated and compensated for with patients on long-term therapy with various diuretic agents.

Animals↗

PubMed1985

Formation of serotonin by rat kidneys in vivo.

Renal formation of serotonin by decarboxylation of its amino acid precursor L-5-hydroxytryptophan (L-5-HTP) has been demonstrated with renal tissue homogenates and isolated perfused rat kidneys. Our objective in the present study was to determine whether the conversion of L-5-HTP to serotonin was associated with functional changes by kidneys in vivo. Renal clearance studies were conducted in anesthetized, volume-expanded male Sprague-Dawley rats receiving either saline (n = 9) or L-5-HTP (15 and 75 micrograms/min iv, n = 9). No change in mean arterial pressure was measured during infusions of L-5-HTP at either dose, whereas glomerular filtration rate (GFR), as measured by the clearance of inulin, and effective renal plasma flow (CPAH) decreased by 34 +/- 5% (mean +/- SE, P less than 0.001) and 26 +/- 7% (P greater than 0.07), respectively. Urine flow and sodium excretion decreased by 41 +/- 9% (P less than 0.01). Serotonin and 5-HTP were determined in urine and plasma using HPLC. High levels of 5-HTP were present in plasma, but not urine. Urinary serotonin increased in the rats receiving L-5-HTP without concomitant increases in plasma serotonin. More than 20% of the infused L-5-HTP was recovered in the urine as serotonin. The decarboxylase inhibitor carbidopa (20 micrograms/min) markedly reduced urinary serotonin excretion in the rats which received L-5-HTP and reversed the changes in GFR, CPAH, urine flow, and sodium excretion. Infusions of the amino acid precursor of L-5-HTP, L-tryptophan (n = 7), did not alter kidney function or increase plasma or urinary 5-HTP or serotonin levels. These results are consistent with the intrarenal formation of serotonin by renal decarboxylase with attendant alterations in renal hemodynamics and salt and water excretion.

5-Hydroxytryptophan↗

PubMed1984

Abnormalities in glomerular function in rats developing spontaneous hypertension.

Clearance and micropuncture studies were conducted on 6-wk-old spontaneously hypertensive rats (SHR) of the Okamoto-Aoki strain and normotensive Wistar-Kyoto rats (WKY) under euvolemic conditions. Mean arterial pressure in SHR was elevated by 18 mmHg and their kidneys were vasoconstricted with reduced blood flow; resistances in preglomerular vessels and efferent arterioles were elevated 2.8 and 2 times, respectively, above WKY values. Whole kidney glomerular filtration rate (GFR) and single nephron glomerular filtration rate (SNGFR), based on fluid collection from either proximal or distal convolutions, were 25-30% lower in SHR. Fractional reabsorptions of fluid load by the proximal convoluted tubule (43%) and by the loop of Henle (52-55%) were similar in both groups. Accordingly, SHR exhibited less fluid delivery from the proximal convolution (8 vs. 12 nl/min) and to the distal convolution (3 vs. 5 nl/min). Glomerular dynamics in hypertensive and normotensive strains were characterized by filtration pressure disequilibrium. Estimated glomerular capillary pressure and mean effective ultrafiltration pressure were similar in SHR and WKY. SHR had a lower glomerular ultrafiltration coefficient than WKY (0.011 vs. 0.016 nl X s-1 X mmHg-1), which, combined with a lower glomerular plasma flow (41 vs. 73 nl/min), quantitatively accounted for the lower SNGFR in 6-wk-old SHR. These findings document important differences in renal function in young SHR compared with WKY that may participate in the development of hypertension.

Absorption↗

PubMed1984

Prolactin and the rat kidney: a clearance and micropuncture study.

PRL is a pituitary hormone with important osmoregulatory properties in lower vertebrates and has been reported to decrease renal water and electrolyte excretion in mammals. Although several studies have suggested that the proximal tubule is the major site of action of PRL, no direct examination of such an effect has been made. In the present study we used micropuncture and clearance techniques to examine the effect of ovine PRL (oPRL) infusion on single nephron and whole kidney function in anesthetized volume-expanded rats pretreated with bromocriptine to suppress endogenous PRL release. oPRL infusion was associated with a significant reduction in urinary sodium, potassium, and water excretion compared to changes seen in the control group. There was no significant effect of oPRL on whole kidney glomerular filtration rate, renal plasma flow, filtration fraction, renal blood flow, renal vascular resistance, or arterial pressure compared to those in control rats. Single nephron studies failed to detect any significant effect of oPRL on single nephron glomerular filtration rate and absolute or fractional reabsorption by the proximal convoluted tubule. Although arginine vasopressin was detected in the oPRL preparation, the quantity infused was negligible compared to the plasma levels found in anesthetized rats prepared for kidney micropuncture. Our results suggest that oPRL exerts a renal tubular action separate from arginine vasopressin to decrease water and electrolyte excretion which occurs beyond the last superficial convolution of the proximal convoluted tubule.

Animals↗

PubMed1984

Serotonin formation in nonblood-perfused rat kidneys.

Infusion of the aromatic L-amino acid decarboxylase substrate L-5-hydroxytryptophan (L-5-HTP) at 1.5, 3.0 and 15 micrograms/min into isolated Krebs-Henseleit-perfused rat kidneys was associated with serotonin output in the urinary and venous effluents. Serotonin was measured by high-performance liquid chromatography using electrochemical detection. Infusion at the two higher doses of L-5-HTP caused marked increases in renal vascular resistance (RVR) of over 80 and 490%, respectively. Administration of the aromatic L-amino acid decarboxylase inhibitor carbidopa (20 micrograms) decreased serotonin output and RVR to base-line levels despite continued infusion of L-5-HTP. Infusion of the D-isomer of 5-HTP at 3 micrograms/min did not significantly alter RVR and produced minimal increases in serotonin output relative to L-5-HTP. These results are consistent with the stereospecific formation of serotonin from its amino acid precursor 5-HTP by whole rat kidney.

5-Hydroxytryptophan↗

PubMed1982

Effects of bromocriptine on single nephron and whole-kidney function in rats.

Bromocriptine (BRC) is a semisynthetic ergot alkaloid possessing dopamine agonistic activity. We had previously observed significant changes in renal hemodynamics in rats pretreated with BRC to suppress endogenous prolactin plasma levels. To investigate further the effects of BRC on single nephron and whole-kidney function, micropuncture and clearance experiments were performed on euvolemic and volume-expanded rats pretreated with BRC (1 mg i.p.) or solvent. Both groups of BRC-pretreated rats had a significantly higher renal plasma flow and a lower arterial pressure, filtration fraction and renal vascular resistance than control (solvent-treated) rats. In volume-expanded rats, BRC caused a small but significant decrease in whole-kidney glomerular filtration rate (GFR) and an increase in superficial single nephron GFR; BRC did not affect GFR or single nephron GFR in euvolemic rats. Proximal tubular reabsorption and urinary excretion of water and electrolytes were not altered by BRC under conditions of euvolemia or volume expansion. It was concluded that BRC exerts a dopamine agonist-like effect to increase renal plasma flow and suppress endogenous plasma prolactin levels, whereas the urinary water and electrolyte excretion and superficial proximal tubular reabsorption are not altered appreciably. The increased ratio of single nephron GFR/GFR suggests that in volume-expanded rats, BRC redistributes glomerular filtration to superficial nephrons, possible by preferential dilation of superficial afferent arterioles.

Animals↗