Blood Flow In Spontaneously Hypertensive Rats Research Articles

Eukaryotic elongation factor 2 kinase inhibitor, A484954 induces diuretic effect via renal vasorelaxation in spontaneously hypertensive rats

Eukaryotic elongation factor 2 (eEF2) kinase (eEF2K), alternatively known as calmodulin-dependent protein kinase III, inhibits protein translation via phosphorylating its sole substrate, eEF2. We previously demonstrated that expression and activity of eEF2K change in mesenteric artery from spontaneously hypertensive rats (SHR) with aging and that eEF2K is involved in pathogenesis of essential hypertension. In addition, we have recently revealed that acute intravenous injection with A484954, a selective eEF2K inhibitor, lowers blood pressure specifically in SHR partly via inducing vasorelaxation. In this study, we examined whether A484954 induces diuretic effect. After male SHR and normotensive Wistar Kyoto rats (WKY) were given a single intraperitoneal injection of A484954 (2.5 mg/kg, 0.5–9 h), urine was collected using metabolic cage. Contraction of isolated renal arteries form SHR was isometrically measured. While A484954 did not induce diuretic effect in WKY, it increased urine output, water intake, and urinary sodium excretion in SHR. A484954 (10 μM) induced vasorelaxation in isolated renal arteries, which was inhibited by a β-adrenergic receptor antagonist, propranolol. It was confirmed that A484954 increased renal blood flow in SHR as measured by renal ultrasonography. In summary, it was for the first time revealed that A484954 induces diuretic effect in SHR at least partly via renal vasorelaxation through β-adrenergic receptor.

Protective effects of tadalafil on prostatic hyperplasia in spontaneously hypertensive rats

We investigated the effects of the phosphodiesterase type 5 inhibitor, tadalafil on prostatic hyperplasia in a hypertensive rat model. Twelve-week-old male spontaneously hypertensive rats (SHRs) were orally treated with tadalafil (2 or 10 mg/kg/day) or vehicle for six weeks. Wistar Kyoto (WKY) rats treated with vehicle were used as controls. The effect of tadalafil was evaluated by measuring prostate weight, blood pressure, and prostatic blood flow. The presence of malondialdehyde (MDA), interleukin-6 (IL-6), transforming growth factor-beta1 (TGF-β1), and basic fibroblast growth factor (bFGF) in the ventral prostate were examined. Hematoxylin and eosin staining was performed to assess the morphological change. The prostatic contractility was evaluated by an organ bath experiment. The vehicle-treated SHRs demonstrated a significantly higher prostate weight, prostate weight/body weight ratio (PBR), blood pressure, and tissue levels of MDA, IL-6, TGF-β1, and bFGF, and lower prostatic blood flow compared to the vehicle-treated WKY rats. Moreover, the SHRs showed glandular morphological abnormalities in the ventral prostate compared to the WKY rats. There was no significant difference in potassium chloride or noradrenaline-induced prostatic contractility between the WKY rats and the SHRs. Treatment with tadalafil decreased prostate weight and PBR in a dose-dependent manner, and improved prostatic blood flow and tissue levels of MDA, IL-6, TGF-β1, and bFGF in SHRs, without affecting the blood pressure. Furthermore, tadalafil ameliorated the glandular morphological abnormalities in the SHR ventral prostate. In conclusion, tadalafil could suppress the prostatic hyperplasia via recovery of reduction in prostatic blood flow in SHRs.

Influence of the renal endothelin system on the autoregulation of renal blood flow in spontaneously hypertensive rats.

The renal endothelin (ET) system has been claimed to play an important role in the regulation of renal blood flow (RBF) and sodium excretion in primary hypertension. The aim of the present study was to investigate the contribution of the endogenous ET system in the autoregulation of total RBF, cortical blood flow (CBF), pressure-dependent plasma renin activity (PRA) and pressure natriuresis in spontaneously hypertensive rats (SHR) by means of the combined (A/B) ET-receptor antagonist, bosentan. In anesthetized rats, RBF was measured by transit-time flow probes and CBF by laser flow probes. During the experiments, the rats received an intrarenal infusion of either bosentan (1 mg/kg/h) or vehicle. Renal perfusion pressure (RPP) was lowered in pressure steps of 5 mm Hg with a servo-controlled electropneumatic device via an inflatable suprarenal cuff. Bosentan had no effect on resting RPP, CBF, PRA and renal sodium excretion, whereas RBF was lowered by 30% (p < 0.05). Furthermore after bosentan the rats revealed a complete loss of RBF autoregulation. In contrast no changes in autoregulation of CBF, pressure-dependent PRA and pressure natriuresis were observed. Our findings demonstrate a significant impairment in total RBF autoregulatory ability during renal ET-receptor blockade which is not confined to the cortical vessels. These data suggest that the renal ET system plays an important role in the dynamic regulation of renal blood flow in SHR.

Effects of exogenous prostacyclin on placental blood flow, placental weight and fetal weight in normotensive and spontaneously hypertensive rats.

Recently, prostacyclin (PGI2) has been used for the treatment of preeclampsia. In this study, we investigated the effects of PGI2 on placental blood flow (measured with clearance of hydrogen gas generated by electrolysis) in normotensive Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). The placental blood flow of PGI2-treated SHR (0.25, 0.5 and 1 mg/kg) was significantly (p less than 0.05) reduced compared with WKY. These data suggest that PGI2 has a certain reducing effect on placental blood flow in SHR; on the other hand, in WKY, it has an increasing effect depending on the dose.

Assessment of muscle blood flow by laser-Doppler flowmetry during hemorrhage in SHR

Skeletal muscle blood flow was assessed via laser-Doppler flowmetry (LDF) in the gracilis muscle of anesthetized 12- to 15-wk-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) control rats subjected to graded hemorrhage. Tissue perfusion was assessed at 20 specific sites in the muscle before and 20 min after each of five successive 1-ml withdrawals of blood. Mean LDF signals recorded from the gracilis muscle of SHR and WKY were similar during the prehemorrhage control period. After hemorrhage, mean arterial pressure and calculated vascular resistance of the gracilis muscle were higher in SHR than in WKY, and SHR exhibited a greater reduction of LDF signal in response to hemorrhage than WKY. Although SHR and WKY had a similar number of low flow sites (LDF signal less than 0.17 V) during the control period, successive blood volume withdrawals led to a significantly greater increase in the number of poorly perfused areas in the muscles of the hypertensive animals. The results of this study suggest that LDF is a useful tool to assess tissue perfusion during circulatory stress and that hemorrhage causes a greater decrease in skeletal muscle blood flow in SHR than in WKY. More severe reductions in tissue perfusion may contribute to the reduced ability of hypertensive animals to survive after hypotensive hemorrhage.

Changes in local cerebral blood flow following bilateral carotid occlusion in spontaneously hypertensive and normotensive rats.

Local blood flow in the cortex and thalamus was measured by the hydrogen clearance method in spontaneously hypertensive rats (SHR) and normotensive rats (NTR) before and after bilateral carotid occlusion. There were no differences in the resting blood flow values between SHR and NTR. Following carotid occlusion cortical blood flow in SHR was markedly reduced to 17% of the resting level at 1 h and, further, to less than 10% at 3--5 h period, while in NTR it decreased only to 36--38% during 5 h occlusion. Thalamic blood flow in SHR was decreased to 39% at 1 hr and to below 20% at 3--5 h, while in NTR it remained approximately 40% of the resting level during 5 h occlusion. The blood flow reduction in either cortex or thalamus after carotid occlusion was much greater in SHR than in NTR. This difference was highly significant. The increased cerebral vascular resistance caused by persistent hypertension may play an important role in a greater reduction of blood flow in SHR after carotid occlusion. Relation of the blood flow reduction to the brain metabolism is discussed.

Rb86 uptake of various organs of the spontaneously hypertensive rats: (a preliminary note).

Twenty spontaneously hypertensive rats (SHR) and 20 control rats were used for measurements of Rb86 uptake of various organs. Hemodynamic measurements and the heart weight to body weight ratio showed a significant and sustained hypertension and increased heart rate in SHR; Ratio of Rb86 uptake in the kidney, brain, liver, adrenal gland, pancreas, and spleen to that in RV was smaller in SHR than that in the control rats. The ratio of Rb86 uptake of inner layer to outer layer of LV, which represents distribution of blood flow to the endocardial layer and epicardial layer, was not different between SHR and the control rats. The fraction of regional flow in the outer and inner cortex, juxtamedulla, and medulla of the kidney was not different between SHR and the control. The present preliminary study may suggest that myocardial blood flow in SHR is greater than that in the control rats. The relationship between cardiac hypertrophy and myocardial flow was discussed.

The hemodynamics of early stages of spontaneous hypertension in rats. Part I: Male study.

Male spontaneously hypertensive rats (SHR) were tested for the cardiac output and organ blood flows at the age 30, 40, 50, 60, 90 and 180 days. The results showed that during the course of developing hypertension in SHR the cardiac output was not elevated. During the prehypertensive period, total peripheral resistance was not elevated, but systolic blood pressure was higher in SHR than in normotensive rats. Increased contractility of the myocardium in SHR was considered to be involved in the pathogenesis of hypertension. Decreased kidney blood flow in SHR after 90 days of age might be related to the high incidence of nephrosclerosis in 180 days old male SHR.