Although insulin release is known to be inhibited by alpha-2 adrenergic agonism, the effect of alpha adrenergic agonism on islet glucagon release remains controversial. Alpha-2 adrenoceptors are subdivided into alpha-2A and alpha-2B subtypes using receptor binding methods or cloning methodology. This study was designed to confirm the involvement of the alpha-2 adrenoceptor and its subtypes in glucagon release from the isolated, perfused rat pancreas. Both the alpha-2A preferential agonist oxymetazoline and the non-subtype-selective alpha-2 agonist clonidine induced concentration-dependent stimulation of glucagon release, starting at 10−8 and 10−7 mol/l, respectively (p<0.01). In contrast, neither of the two alpha-1 selective agonists, methoxamine and phenylephrine, at concentrations up to 10−6 mol/l affected glucagon release. Furthermore, the non-subtype-selective alpha-2 antagonist rauwolscine at concentrations of 10−6 and 10−5 mol/l and the alpha-1 and alpha-2A selective antagonist WB-4101 at 10−5 mol/l showed significant antagonism of 10−7 mol/l clonidine-induced glucagon release versus corresponding controls. Neither the alpha-1 and alpha-2B selective antagonist prazosin nor the alpha-2B preferential antagonist chlorpromazine, at concentrations up to 10−5 mol/l, antagonized the effects of clonidine. None of the eight drugs, at the concentrations tested, affected insulin release with 5.5 mmol/l glucose. These results suggest that in rats islet glucagon release induced by alpha adrenoceptor agonism is mediated through alpha-2 adrenoceptors, possibly the alpha-2A subtype.
Hiroshi Hirose, Hiroshi Maruyama, Katsuhiko Itoh, Kazunori Koyama, Koichi Kido and Takao Saruta
Yoshihiko Saito, Kazuwa Nakao, Akira Sugawara, Kazunobu Nishimura, Makoto Sakamoto, Narito Morii, Takayuki Yamada, Hiroshi Itoh, Shozo Shiono, Takanobu Kuriyama, Masashi Hirai, Motoharu Ohi, Toshihiko Ban and Hiroo Imura
Abstract. The plasma concentration of atrial natriuretic polypeptide was measured in eight healthy men during two grades of exercise performed in the supine position on a bicycle ergometer. The plasma concentration of atrial natriuretic polypeptide slightly increased during the first exercise test with 20% of the maximal oxygen uptake and it approximately doubled during the second exercise with 40% of the maximal oxygen uptake (from 15.5 ± 5.5 (mean ± sd) pmol/l to 31.8 ± 10.7 pmol/l). The increase in the plasma level of atrial natriuretic polypeptide in the second exercise was significantly greater than that in the first one. The plasma norepinephrine level and plasma renin activity showed significant increases during the second exercise test. Heart rate and systolic blood pressure also increased in response to the graded exercise. The increase in the plasma concentration of atrial natriuretic polypeptide during exercise was significantly correlated with the increase in heart rate, systolic blood pressure, and the plasma norepinephrine concentration (r = 0.75, r = 0.71 and r = 0.51, respectively). These results indicate that the plasma concentration of atrial natriuretic polypeptide increases in response to the intensity of a workload, and suggest that exercise is a useful test to evaluate the releasing function of atrial natriuretic polypeptide in the heart.
Akiyuki Kawashima, Masakatsu Sone, Nobuya Inagaki, Yoshiyu Takeda, Hiroshi Itoh, Isao Kurihara, Hironobu Umakoshi, Takamasa Ichijo, Takuyuki Katabami, Norio Wada, Yoshihiro Ogawa, Junji Kawashima, Megumi Fujita, Shozo Miyauchi, Shintaro Okamura, Tomikazu Fukuoka, Toshihiko Yanase, Shoichiro Izawa, Yuichiro Yoshikawa, Shigeatsu Hashimoto, Masanobu Yamada, Tatsuya Kai, Tomoko Suzuki, Mitsuhide Naruse and the JPAS and JRAS groups
Several clinical studies have reported that renal impairments are sometimes observed in patients with primary aldosteronism (PA). We analyzed the prevalence of renal impairments in PA patients and identified parameters that increase the risk for them.
This is a retrospective cross-sectional study. We assessed the PA database established by the multicenter Japan PA study (JPAS). Data were also collected from patients with essential hypertension (EHT).
We compared the prevalences of proteinuria and lowered estimated glomerular filtration rate (eGFR) between patients with PA and age, sex, blood pressure and duration of hypertension-matched patients with EHT. We also performed logistic regression analysis to identify parameters that increase the risk for these renal impairments.
Among 2366 PA patients, the prevalences of proteinuria and lowered eGFR were 10.3 and 11.6%, respectively. The prevalence of proteinuria was significantly higher in PA patients than matched-EHT patients (16.8 vs 4.4%), whereas there was no significant difference in the prevalence of lowered eGFR (17.2 vs 15.0%). The logistic regression analysis also showed that the plasma aldosterone concentration (PAC) significantly increases the risk of proteinuria and lowered eGFR, independent of other known risk factors.
Plasma aldosterone levels are closely associated with renal impairment in patients with PA. This is contrast to our earlier finding that the PAC was not itself linearly associated with cardiovascular events such as stroke or ischemic heart disease. The mechanism underlying the kidney damage in patients with PA may differ from that affecting the cardiovascular system.
Hiroki Kobayashi, Yoshihiro Nakamura, Masanori Abe, Isao Kurihara, Hiroshi Itoh, Takamasa Ichijo, Yoshiyu Takeda, Takashi Yoneda, Takuyuki Katabami, Mika Tsuiki, Norio Wada, Yoshihiro Ogawa, Ryuichi Sakamoto, Junji Kawashima, Masakatsu Sone, Nobuya Inagaki, Takanobu Yoshimoto, Tetsuya Yamada, Ryuji Okamoto, Yuichi Matsuda, Megumi Fujita, Minemori Watanabe, Kouichi Tamura, Akiyo Tanabe, Mitsuhide Naruse and JPAS/JRAS Study Group
We investigated the clinical significance of ACTH stimulation during adrenal venous sampling (AVS) by surgical outcome of primary aldosteronism (PA).
Multicenter retrospective study by Japan PA study.
We allocated 314 patients with both basal and ACTH-stimulated AVS data who underwent adrenalectomy to three groups: basal lateralization index (LI) ≥2 with ACTH-stimulated LI ≥4 on the ipsilateral side (Unilateral (U) to U group, n = 245); basal LI <2 with ACTH-stimulated LI ≥4 (Bilateral (B) to U group, n = 15); and basal LI ≥2 with ACTH-stimulated LI <4 (U to B group, n = 54). We compared surgical outcomes among the groups using the Primary Aldosteronism Surgical Outcome (PASO) criteria.
Compared with U to U group, U to B group had poor clinical and biochemical outcomes and low rates of adrenal adenoma as pathological findings (P = 0.044, 0.006, and 0.048, respectively), although there were no significant differences between U to U and B to U groups. All patients in U to B group with clinical and biochemical benefits, however, had adrenal adenoma as pathological findings and could be well differentiated from those with poor surgical outcomes via basal LI (>8.3), but not ACTH-stimulated LI. These results were similar even when we defined each group based on a cut-off value of 4 for basal LI.
Although PA patients in U to B group had worse surgical outcomes than did those in U to U group, basal LI could discriminate among patients with better surgical outcomes in U to B group.