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Biomedical subjects

C T Stier

Publications and source records attributed to C T Stier.

At least 19 recordsLinked to original sources

GM1 ganglioside treatment of spontaneously hypertensive stroke prone rats.

Many reports indicate that GM1 ganglioside is effective in reducing CNS ischemic injury in animal models. These models employ invasive surgery to induce ischemic damage in otherwise healthy animals. The purpose of this study was to determine if the beneficial effects of GM1 could be generalized to Spontaneously Hypertensive Rats-Stroke Prone (SHRSP). The SHRSP strain develops a pathology similar to those observed in patients with stroke. The SHRSP have "risk" factors that include hypertension, fibrinoid necrosis, and sensitivity to diet. Female SHRSP were randomly assigned to GM1- or saline-treatment conditions. Rats were fed a stroke-inducing diet. Daily body weights, weekly blood pressure, time of stroke onset, and age at death were recorded. Spontaneous activity and performance on a tail-hang test were assessed thrice weekly. The results indicate that GM1 treatment did not delay the time of stroke onset or death. GM1 did reduce hyperactivity in the initial stages of the ischemic pathology, but did not prevent the marked decline in behavioral activity observed at later time points. There were no differences in weight loss, performance on the tail-hang test, or number of CNS injury-related symptoms observed. These findings suggest that GM1 was not as effective in decreasing mortality, weight loss, or behavioral deficits in SHRSP as previously reported using other animal models of ischemia. Distinguishing between those animal models in which GM1 is more and less effective may be useful in determining under which clinical situations GM1 is likely to be most suitable.

Aging

Stroke prevention by losartan in stroke-prone spontaneously hypertensive rats.

BACKGROUND: Chronic angiotensin converting enzyme (ACE) inhibitor therapy with enalapril, captopril or ceranopril prevents the development of cerebrovascular lesions in stroke-prone spontaneously hypertensive rats (SHRSP) given a 1% NaCl solution to drink, with little or no effect on systolic blood pressure. OBJECTIVES: To determine the effect of the orally active angiotensin (Ang) II receptor antagonist losartan on blood pressure and stroke in SHRSP. METHODS: Losartan or vehicle was chronically administered to saline-drinking SHRSP, and systolic blood pressure was monitored. The effect of losartan on arterial blood pressure measured by radiotelemetry in enalapril-treated SHRSP was also examined. RESULTS: Oral losartan at 30 mg/kg per day delayed the development of severe hypertension and prevented stroke in saline-drinking SHRSP. Losartan therapy at a dose of 10 mg/kg per day did not affect the systolic blood pressure elevation but prevented the occurrence of cerebrovascular lesions at least until 28 weeks of age. Radiotelemetric monitoring of arterial blood pressure in enalapril-treated, saline-drinking SHRSP over a 3-month period verified the maintenance of severe hypertension without any strokes. Treatment with oral losartan at a dose of 30 mg/kg did not affect the blood pressure of SHRSP chronically treated with enalapril. CONCLUSIONS: These results are consistent with the theory that Ang II has an effect on the pathophysiology of cerebrovascular lesion development in saline-drinking SHRSP. These findings indicate that losartan has a protective action, similar to that previously observed with ACE inhibitors, against the development of cerebrovascular lesions in SHRSP in the absence of a blood pressure fall.

Angiotensin Receptor Antagonists

Enhanced vasodilatory responses to bradykinin in stroke-prone spontaneously hypertensive rats.

Vasodilatory responses to bradykinin (BK) and acetylcholine (ACh) were compared in phenylephrine preconstricted perfused kidneys from 30-week-old male stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY). Responses to ACh did not differ between kidneys from SHRSP and WHY. BK-induced dilatation was greater in kidneys from SHRSP relative to WHY and was not affected by indomethacin or captopril. These results indicate that renal vasodilatory responsiveness to bradykinin is enhanced in SHRSP with established hypertension.

Acetylcholine

Enhanced thromboxane formation by blood but not whole platelets from spontaneously hypertensive rats.

Increased serum levels of immunoreactive thromboxane B2 (iTXB2) were observed in spontaneously hypertensive rats of the Okamoto-Aoki strain (SHR) compared with normotensive Wistar-Kyoto rats (WKY). Serum iTXB2 levels in whole blood allowed to clot at 37 degrees C for 1 hour were significantly greater in SHR than WKY at 8, 16-20, and 38 weeks of age, whereas formation of iTXB2 by thrombin-stimulated whole platelets from 6 16-week-old SHR and 6 age-matched WKY was 399 +/- 44 and 377 +/- 38 ng/10(9) platelets/30 min, respectively. No significant difference in radioconversion of exogenous arachidonic acid to TXB2 was observed in whole platelets from SHR (18.2 +/- 2.5%, n = 4) and WKY (20.1 +/- 3.0%, n = 4) at 16 weeks of age. These results support the proposal that enhanced ability of blood from SHR to generate iTXB2 is independent of the stage of hypertension development. This enhancement probably depended on factors or blood elements other than platelets since no difference in formation was observed on stimulation of whole platelets.

Animals

The lipoxygenase inhibitor phenidone protects against proteinuria and stroke in stroke-prone spontaneously hypertensive rats.

The present study examined whether the dual cyclooxygenase/lipoxygenase inhibitor phenidone would protect stroke-prone spontaneously hypertensive rats (SHRSP) from stroke and hypertensive renal disease. Vehicle-treated SHRSP (N = 6), fed stroke-prone rodent diet and 1% saline, exhibited severe systolic blood pressure elevation (261 +/- 10 mm Hg, mean +/- SEM), marked proteinuria (90 +/- 12 mg/day), and stroke, with an average age at death of 14 +/- 1 weeks. In a second group of six saline-loaded SHRSP, treatment with phenidone (60 mg/kg/day) was started at 8.4 weeks of age. Despite establishment of severe hypertension in this group (274 +/- 10 mm Hg), proteinuria remained at basal levels (28 +/- 13 mg/day), and signs of stroke were absent (P less than .01 v vehicle) through at least 16 weeks of age. Phenidone treatment also prevented the declines in body weight and food intake observed in vehicle-treated SHRSP, and maintained urine volume and saline intake. Serum 12-hydroxy-eicosatetraenoic acid (12-HETE) generation was significantly inhibited greater than 50% in incubates of whole blood from phenidone-treated SHRSP. We have previously shown that agents which interfere with the renin-angiotensin system afford protection from renal and cerebrovascular injury in saline-loaded SHRSP; cyclooxygenase inhibition alone will hasten the onset of these pathologic changes. Whether phenidone, which has been reported to attenuate angiotensin II-mediated effects, affords vascular protection by interference with a lipoxygenase-mediated action of angiotensin II remains to be elucidated.

Animals

The antiproteinuric action of enalapril in stroke-prone spontaneously hypertensive rats is unrelated to alterations in urinary prostaglandins.

We examined whether the renal protective effect of the angiotensin I converting enzyme inhibitor enalapril in stroke-prone spontaneously hypertensive rats (SHRSP) is dose-related and associated with alterations in the urinary excretion of prostaglandin (PG) E2 and 6-keto-PGF1 alpha, a stable breakdown product of prostacyclin. Enalapril maleate at 1.5, 5 and 15 mg/kg/day or vehicle was chronically administered to saline-drinking SHRSP (six per group) starting at 8.1 weeks of age. Vehicle-treated SHRSP developed severe hypertension, proteinuria and strokes (age at death, 14 +/- 1 weeks; mean +/- S.E.). Enalapril prolonged survival dose-dependently and reduced proteinuria; all SHRSP given 15 mg/kg/day lived beyond 23 weeks of age without evidence of stroke or proteinuria. There was no effect of enalapril at any dose on systolic arterial blood pressure in spite of variable levels of urinary protein excretion and onset of stroke in the different groups. Likewise, urinary 6-keto-PGF1 alpha and PGE2 excretion did not differ among the groups except for an increase in 6-keto-PGF1 alpha in the 15 mg/kg/day group at one week after initiation of enalapril therapy. These results are consistent with a dose-related renal protective action of enalapril in saline-drinking SHRSP that is not closely associated with sustained alterations in urinary excretion of renal vasodilatory PGs.

Animals

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

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

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

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

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

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

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

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

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

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

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

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