Increase In RBF Research Articles

Once a day indapamide therapy in hypertension. Effects on the heart and peripheral arterial circulation.

Indapamide, a sulphonamide derivative, was prescribed for 8 weeks at low dose (2.5 mg once a day) to 14 hypertensive patients in order to investigate its effects on systolic and diastolic blood pressure (SBP, DBP), cardiac function and peripheral arterial resistance (PAR). During treatment we observed decreases in both SBP and DBP without any change in HR in the supine and standing positions and on exercise. As a result cardiac work was significantly reduced. Slight changes in pre-ejection period (PEP) and left ventricular ejection time (LVET) along with a more significant decrease in rate of rise of left ventricular pressure (DBP to PEP ratio) were observed during treatment. An increase in RBF and a decrease in PAR were also detected in the peripheral circulation. These findings may indicate that indapamide antagonizes the cardiovascular effects of catecholamines.

Effects of prostaglandin I2 and E2 on renal hemodynamics and function and renin release.

The effects of PGI2 and PGE2, given in the same doses were compared as to renal hemodynamics and functions and renin release. The same experimental conditions were used for both compounds and experiments were carried out in pentobarbital anesthetized dogs. Adrenergic influences were excluded by renal denervation. Given intrarenally at doses at 0.1 microgram/min and 1 microgram/min, PGE2 caused significant increase in RBF, UF and UNaV, but had no effect on BP and GFR. Intrarenal infusion of PGI2 at a rate of 1 microgram/min resulted in a significant increase of RBF and in a marked fall of BP, but only little change in GFR, UF and UNaV. With a dose of 0.1 microgram/min, the parameters remained the same. Intravenous infusion of PGI2 (1 microgram/min) caused a significant fall in BP with no change in the other parameters. Both PGI2 and PGE2 had a similar effect on intrarenal hemodynamics, i.e., caused a progressively greater proportional vasodilation from superficial to deep cortex. Given intrarenally in a dose of 1 microgram/min, PGI2 and PGE2 increased renin release. But with a dose of 0.1 microgram/min and 1 microgram/min, i.v., renin secretion was not influenced. The effect of PGI2 on systemic blood pressure was more potent than that of PGE2, however, with regard to renal vasodilating action and tubular effects, PGE2 was the more potent. Present data indicate that PGI2 and PGE2 stimulate renin secretion through a direct action on the juxtaglomerular cells.

Effects of calcium ionophore, A23187, on prostaglandin E2 and renin release in dogs.

Effects of calcium ionophore, A23187, on prostaglandin E2 and renin release, and the interrelationship were investigated in anesthetized dogs. PGE2 concentration in arterial and renal venous plasma was measured by radioimmunoassay, and secretion rate (pg/g-min) from the kidney was calculated. The renin secretion rate (ng/g-min) was calculated simultaneously. Intrarenal infusion of A23187 at a rate of 0.5 mg/min for 2 min resulted in a significant increase in RBF. PGE2 secretion rate increased from 61 +/- 26 to 1012 +/- 566 1222 +/- 500 and 388 +/- 125 at 5, 9 and 17 min. Renin secretion rate also increased rom 1.4 +/- 0.8 to 2.3 +/- 1.3, 5.8 +/- 2.7 and 5.9 +/- 1.6 at 5, 9 and 17 min. However, systemic administration of A23187 at a rate of 0.5 mg/min for 2 min did not alter the parameter. Thus, intrarenal infusion of A23187 affects RBF, renin release and PGE2 release directly within the kidney. In indomethacin treated dogs (5 mg/kg, i.v.) intrarenal infusion of A23187 significantly decreased RBF. The renin release with A23187 was also abolished with indomethacin as well as PGE2 release. These results suggest that calcium mobilization within the kidney plays an important role in PGE2 synthesis and release, and that the renal vasodilation and renin release are secondary effects of renal PGs synthesis and release.

The role of hypothalamo-sympathetic nerve system to maintain high blood pressure in DOCA hypertensive rats.

Effects of calcium ionophore, A23187, on prostaglandin E2 and renin release, and the interrelationship were investigated in anesthetized dogs. PGE2 concentration in arterial and renal venous plasma was measured by radioimmunoassay, and secretion rate (pg/g·min) from the kidney was calculated. The renin secretion rate (ng/g·min) was calculated simultaneously. Intrarenal infusion of A23187 at a rate of 0.5 mg/min for 2 min resulted in a significant increase in RBF. PGE2 Secretion rate increased from 61 ± 26 to 1012 ± 566 1 222 ± 500 and 388 ± 125 at 5, 9 and 17 min. Renin secretion rate also increased from 1.4 ± 0.8 to 2.3 ± 1.3, 5.8 ± 2.7 and 5.9 ± 1.6 at 5, 9 and 17 min. However, systemic administration of A23187 at a rate of 0.5 mg/min for 2 min did not alter the parameter. Thus, intrarenal infusion of A23187 affects RBF, renin release and PGE2 release directly within the kidney. In indomethacin treated dogs (5 mg/kg, i.v.) intrarenal infusion of A231 87 significantly decreased RBF. The renin release with A23187 was also abolished with indomethacin as well as PGE2 release. These results suggest that calcium mobilization within the kidney plays an important role in PGE2 Synthesis and release, and that the renal vasodilation and renin release are secondary effects of renal PGs Synthesis and release.

1108 AMELIORATION OF COMPENSATORY CHANGES AFTER RELEASE OF UNILATERAL URETERAL OCCLUSION

Following release of unilateral ureteral occlusion (UUO), the adaptive changes which occur in the contralateral kidney have been poorly documented and the mechanisms involved in these compensatory changes are unknown. In the present study, rats were subjected to 24 hrs of UUO, and adaptive changes in the contralateral kidney were studied after relief of UUO.Twenty-four hrs after release of UUO, the contralateral kidney had a massive increase in GFR (1020±63 μl/min/100gmBW) and RBF (4552±490 μl/min/100gmBW) compared to sham-operated controls (GFR 595±18; RBF 2745±275, P<0.001 for both). Similar but less impressive compensatory changes occurred in rats with unilateral nephrectomy or unrelieved UUO (GFR 712±39, RBF 3330±227, P<0.05). The infusion of indomethacin (10 mg/kg) completely eliminated the adaptive changes in rats with relieved UUO (GFR 592±63, RBF 2892±245, P<0.001) but had no effect on sham-operated controls (GFR 578±18, RBF 2801±313, P = NS).These data indicate that impressive adaptive changes in GFR and RBF occur in the contralateral kidney 24 hrs after release of UUO. The inhibition of these compensatory changes by infusion of indomethacin suggests that the increase in GFR and RBF may be mediated via release of prostaglandins from the previously obstructed kidney.

Effects of secretin on renal functions in the dog

In anesthetized mongreal dogs, the intrarenal arterial (0.2 approximately 1.0 unit/kg-min) and the intravenous infusion (0.4 approximately 2.0 unit/kg-min) of secretin caused dose-dependent increase of RBF, accompanied by decreases of the calculated afferent arteriolar resistance (Ra) and efferent arteriolar resistance (Re), but produced no significant effect on GFR, urine flow, electrolyte excretion, osmolar clearance and free water reabsorption. The distribution of cortical blood flow was examined using the radioactive microsphere technique. The intrarenal infusion of secretin (1.0 unit/kg-min) increased renal cortical blood flow in the juxtamedullary area much more than in the superficial area, shifting the blood flow from the outer to the inner zone. Simultaneous intrarenal infusion of secretin (1.0 unit/kg-min) and glucagon (0.5 microng/kg-min) produced increases in GFR, urine flow and electrolyte excretion to a lesser degree than those induced by glucagon alone, whereas the increment in RBF and the decreases in Ra and Re were almost to the same degree as those caused by secretin alone. The present results indicate that secretin produces the dilation of afferent and efferent arterioles, resulting in an increase in RBF, with no change in GFR and urine flow, and that the effects of glucagon on renal functions are masked by secretin mainly through the effects of renal hemodynamics.

Inhibiton of Furosemide Induced Increase in Renal Blood Flow by Indomethacin

SummaryThe ability of furosemide to increase RBF was found to be significantly inhibited by indomethacin. The implication of this observation is that the dilation of the renal vasculature produced by furosemide is mediated by prostaglandins. Inhibition of the synthesis of these agents by indomethacin inhibits the increase in RBF produced by furosemide.

Effects of prostaglandin B2 on renal hemodynamics and excretion.

Summary and ConclusionThe infusion of PGB2 into canine renal arteries produces a dose related increase in total RBF and UNaV. The increasing variability in RBF and NNaV with increasing dose may be due to a transition from vasodilator to vasoconstrictor action. The results obtained demonstrate that PGB2 affects renal hemodynamics and excretion qualitatively the same as PGE1, PGE2, PGA1 and PGA2.

Effects of secretin on renal hemodynamics and excretion.

SummaryThe infusion of secretin directly into a renal artery produced a dose related increase in RBF and CPAH and reduction in RVR. V and TcH2O were unaffected and no increase in UNaV was observed. This is surprising because dilators of renal vasculature produce a natriuresis which correlates with the increase in RBF.

STUDIES ON THE EFFECTS OF LONG-TERM TREATMENT WITH HYPOTENSIVE DRUGS IN PATIENTS OF ESSENTIAL HYPERTENSION

Since the introduction of various hypotensive drugs into the clinical use for treatment of essential hypertension, many advantages have been expected for the prognosis in hypertensive patients. At present, however, very few reports are found about long-term observation on the effects of continuous therapy. No systematic investigation has been reported on changes in RBF, retinal findings and ECG in numbers of patients, which were resulted from the prolonged blood pressure reduction. In this study, 165 patients with moderate or severe essential hypertension were treated with various hypotensive drugs over the periods of 6 to 46 months continuously, and the hypotensive responses, changes in maintenance dosage of drugs, and effects on RBF, retinal findings and ECG were observed and following results were obtained. The percentages of effective cases, in which the continued blood pressure reduction exceeding 20/10 mmHg below pretreatment control levels was achieved by the single therapy, were 30% with Rauwolfia alkaloids, 29% with Veratrum alkaloids, 50% with hydralazine, 38% with hexamethonium and 50% with pentolinium. In the combined therapy, the above described hypotensive effects of Rauwolfia plus Veratrum alkaloids, Rauwolfia plus hydralazine, Rauwolfia plus hexamethonium, Rauwolfia plus pentolinium, and Rauwolfia plus hexamethonium or pentolinium plus hydralazine were observed in 40%, 55%, 76%, 81% and 91% of patients respectively. The combined therapy seems in general more effective than the single therapy so far as the hypotensive effects are concerned. Maintenance dosages of hypotensive agents were observed to have a tendency to decrease with duration of treatment when sufficient reduction of blood pressure was maintained. Daily requirements of drugs in summer were about 50 to 80% of those in winter. Of 79 treated patients, 31 cases (39%) showed significant increase in RBF measured by PAH clearance method, and 10 cases (13%) showed decrease in RBF after treatment. It was observed that the longer the duration of treatment the larger the percentage of cases whose RBF increased by the therapy. This percentage was also found to be larger in cases which maintained sufficient blood pressure reduction. In 22 cases (18%) of 124 treated patients, retinal findings showed improvement in grade of Keith-Wagener classification, while their aggravation was seen in 4 cases (3%). The rate of improvement increased with duration of treatment, and was larger in cases with good hypotensive response.ECG findings were improved in 28 cases (44%) of 63 treated patients and worsend in 5 cases (8%). The rate of improvement was larger in cases which maintained sufficient hypotensive response and it increased with duration of therapy. Improvement of ECG findings appeared relatively earlier comparing with that of RBF or retinal findings. It is concluded that adequate and prolonged treatment with hypotensive agents results in significant improvements of objective manifestations of various organs including the kidney, fundi and the heart in patients with essential hypertension.