Involvement of complement 3 in the salt-sensitive hypertension by activation of renal renin-angiotensin system in spontaneously hypertensive rats.

We previously showed that complement 3 (C3) is highly expressed in mesenchymal tissues in spontaneously hypertensive rats (SHR). We targeted C3 gene by zinc-finger nuclease (ZFN) gene-editing technology and investigated blood pressure and phenotype in SHR. Blood pressure was measured by tail-cuff and telemetry methods. Histology and expression of liver X receptor α (LXRα), renin, Krüppel-like factor 5 (KLF5), and E-cadherin were evaluated in kidneys. Mesangial cells (MCs) were removed from glomeruli from three strains, and we evaluated the phenotype in vitro. SHR showed the salt-sensitive hypertension that was abolished in C3 knockout (KO) SHR. Proliferation of MCs from SHR was higher than that from Wistar-Kyoto (WKY) rats and showed a synthetic phenotype. Renal injury scores were higher in SHR than in WKY rats and C3 KO SHR. Expression of E-cadherin was lower, and expression of renin was higher in the nephrotubulus from SHR than WKY rats and C3 KO SHR. Expression of C3 α-chain protein and α-smooth muscle actin protein was significantly higher in renal medulla from SHR than from WKY rats. Expression of angiotensinogen, LXRα, renin, and KLF5 mRNA was increased in kidney from SHR compared with C3 KO SHR. Intrarenal angiotensin II levels were significantly higher in kidney from SHR than WKY rats and C3 KO SHR. Urinary epinephrine and norepinephrine excretions were significantly higher in SHR than in WKY rats and C3 KO SHR. These findings showed that increased C3 induces salt-sensitive hypertension with increases in urinary catecholamine excretion and intrarenal activation of the renin-angiotensin system by the dedifferentiation of mesenchymal tissues in kidney from SHR.

Acute effects of physical exercise on prefrontal cortex activity in older adults: a functional near-infrared spectroscopy study.

We examined the acute effect of physical exercise on prefrontal cortex activity in older adults using functional near-infrared spectroscopy (NIRS). Fourteen older adults visited our laboratory twice: once for exercise and once for the control condition. On each visit, subjects performed working memory tasks before and after moderate intensity exercise with a cycling ergo-meter. We measured the NIRS response at the prefrontal cortex during the working memory task. We found that physical exercise improved behavioral performance of the working memory task compared with the control condition. Moreover, NIRS analysis showed that physical exercise enhanced the prefrontal cortex activity, especially in the left hemisphere, during the working memory task. These findings suggest that the moderate intensity exercise enhanced the prefrontal cortex activity associated with working memory performance in older adults.

Enhanced response from the caudal pressor area in spontaneously hypertensive rats.

The caudal pressor area (CPA), located in the caudal extension of the ventrolateral medulla, tonically activates the rostral ventrolateral medulla (RVLM) vasomotor neurons and regulates arterial pressure (AP) in normotensive animals. It is well established that sympathoexcitatory outflow from the RVLM in spontaneously hypertensive rats (SHR) is elevated compared to normotensive animals. Several studies have reported different cardiovascular responses to pharmacological alteration of the RVLM in SHR. Although the CPA may be one of the sources of presympathoexcitatory influence to the RVLM vasomotor drive in normotensive animals, it is unclear whether hypertensive animals such as SHR differ in their response to vasomotor drive evoked from the CPA. In this study, we examined whether sympathoexcitatory influence evoked from the CPA is enhanced in SHR. Local injection of glutamate into the CPA of chloralose-anesthetized male SHR elicited a substantially greater pressor response than in Wistar-Kyoto (WKY) rats, whereas the pressor response evoked by local injection of glutamate into the RVLM was the same in both strains. Furthermore, injection of glycine into the CPA decreased blood pressure to a greater extent in SHR than in WKY rats. These results suggest that the sympathoexcitatory influence of the CPA is enhanced in SHR. Therefore, the enhancement of sympathoexcitatory vasomotor drive evoked from the CPA may, at least in part, support elevated AP and regulate sympathetic tone in this hypertensive model.

A case of adrenocorticotropin-independent bilateral adrenal macronodular hyperplasia (AIMAH) with primary hyperparathyroidism (PHPT).

We report a rare case of ACTH-independent macronodular adrenal hyperplasia (AIMAH) with primary hyperparathyroidism (PHPT). A 57-year-old woman was admitted to our hospital for further examination of secondary hypertension and bilateral adrenal macrotumors. Midnight serum cortisol elevation with undetectable plasma ACTH, increased 24-hour urinary free cortisol excretion, and loss of the normal circadian rhythm in cortisol secretion established the diagnosis of Cushing's syndrome. Total resection of the enlarged left adrenal gland was performed with subsequent steroid replacement. Her general condition improved but serum calcium level increased 3 weeks after surgery. PHPT was diagnosed on the basis of endocrinological examination, although imaging studies failed to detect parathyroid lesion. In summary, we believe this to be the first report of a case of AIMAH with PHPT.

Ventrolateral medulla AT1 receptors support arterial pressure in Dahl salt-sensitive rats.

The present study addresses the hypothesis that angiotensin type 1 receptors (AT1Rs) in the rostral ventrolateral medulla (RVLM) contribute to the elevation of mean arterial pressure (MAP) in Dahl salt-sensitive (DS) rats fed a diet with a high NaCl content. Groups of DS or Dahl salt-resistant (DR) rats were fed diets containing either 0.3% NaCl (LNa) or 8% NaCl (HNa) for 3 weeks. Rats were anesthetized with alpha-chloralose, and the effects of microinjecting the AT1R antagonist valsartan (Val) or angiotensin II (Ang II) into the RVLM on MAP were measured. Bilateral injection of 100 pmol Val into the RVLM reduced the elevated MAP in the DS-HNa rats by approximately 35 mm Hg. In contrast, Val had no effect on MAP in DS-LNa rats. DR rats were normotensive on either diet; Val injection into the RVLM had no significant effect on MAP in DR-HNa rats but did evoke a small decrease in MAP in DR-LNa rats. Injection of Ang II into the RVLM increased arterial pressure in all groups, but the response was substantially larger in DS-HNa rats. Inhibition of neuronal function in the vicinity of the hypothalamic paraventricular nucleus, a possible source of innervation of the RVLM AT1R, by local injection with muscimol also produced a substantial decrease in MAP in DS-HNa rats but not in DS-LNa rats or DR rats. Thus, RVLM AT1Rs appear to contribute to salt-dependent hypertension in DS rats, and the paraventricular nucleus may be a source of this tonic activation.

Ventrolateral medulla AT1 receptors support blood pressure in hypertensive rats.

Angiotensin within the central nervous system appears to be important for the maintenance of hypertension in spontaneously hypertensive rats. This study addresses the hypothesis that blockade of AT1 receptors in the rostral ventrolateral medulla would decrease blood pressure in spontaneously hypertensive rats and that this tonically active AT1-mediated input to the rostral ventrolateral medulla arises from the hypothalamic paraventricular nucleus. Injection of the nonpeptide AT1 receptor antagonist valsartan bilaterally into the rostral ventrolateral medulla of choralose-anesthetized adult spontaneously hypertensive rats produced a dose-related decrease in mean arterial pressure, with a maximal effect of approximately 30 mm Hg. Inhibition of the paraventricular nucleus by local injection of muscimol elicited a similar response, which was inhibited by prior injection of valsartan into the rostral ventrolateral medulla. In contrast, in control Wistar-Kyoto rats, neither valsartan injected into the rostral ventrolateral medulla nor muscimol injected into the paraventricular nucleus had a substantial effect on arterial pressure. These data indicate that in spontaneously hypertensive rats but not in Wistar-Kyoto rats, rostral ventrolateral medulla vasomotor neurons are tonically excited by endogenous stimulation of AT1 receptors, and this input is apparently driven from the hypothalamus. These results suggest that the rostral ventrolateral medulla is one site that the brain renin-angiotensin system acts to maintain elevated blood pressure in spontaneously hypertensive rats.