The effects of substance P (SP) on the membrane and contractile properties of the smooth muscle cell, or on neuro‐effector transmission in the guinea‐pig ileum were observed by means of microelectrodes, double sucrose gap and tension recording. SP (10−13‐10−10 M) induced a phasic contraction of longitudinal muscle strips, but did not change the muscle tone of circular muscle strips, in concentrations up to 10−8 M. SP (1010‐10‐8M) evoked three different membrane responses in longitudinal muscle cells: (i) bursts of spike discharges with no significant change in the membrane potential and input membrane resistance; (ii) bursts of spike discharges with a small but clear depolarization of the membrane and increase in the input membrane resistance; (iii) slow waves with no change in the membrane potential. In the circular muscle cells, low concentrations of SP (< 10−8M) did not affect the membrane potential or the spikes, but SP (10−7M) increased the spike discharges with no significant change in the membrane potential. SP (10−10M) reduced the threshold depolarization required for the generation of action potentials with no change in membrane potential of the longitudinal muscle cells. Pretreatment with atropine (5 × 10−6M), tetrodotoxin (TTX 10−6M) or baclofen (4.7 × 10−6M) had no effect on the excitatory actions of SP on the smooth muscle cells of longitudinal and circular muscle strips. Excitatory actions of SP on the membrane potential or spike activities of longitudinal muscle cells were preserved in NaCl but not in Ca‐deficient solution. SP (10−10‐10−9M) enhanced the amplitude of the excitatory junction potentials (e.j.ps) evoked by electrical field stimulation in longitudinal muscle cells with no change in the membrane potential and input resistance. SP (10−10‐10−9M), however, did not change the amplitude of inhibitory junction potentials (i.j.ps) recorded from the circular muscle cells. These results indicate that SP in relatively low concentrations acts on both smooth muscle cells and on excitatory neuro‐effector transmission in the longitudinal muscle; the main site of the action of SP is probably the muscle membrane.

SummaryMany patients still have high blood pressure (BP) after treatment with angiotensin II type 1 (AT 1 ) receptor blockers (ARBs). We compared the efficacy and safety of azilsartan to those of olmesartan in a prospective randomized clinical trial. Sixty-four hypertensive patients who were treated with ARBs other than azilsartan and olmesartan were enrolled in this study. We randomly assigned patients to changeover from their prior ARBs to either azilsartan or olmesartan, and followed the patients for 3 months. Systolic BP (SBP) in the azilsartan group was significantly decreased at 3 months, and diastolic BP (DBP) and pulse rate (PR) in the olmesartan group showed significant reductions after 3 months. There were no significant differences in ΔSBP, ΔDBP, or ΔPR (Δ = the value at 3 months minus the value at 0 months) between the groups. Serum levels of creatinine (Cr), uric acid (UA), and potassium (K) in the azilsartan group significantly increased after 3 months. While the changes in Cr, UA, and K were within the respective normal ranges, ΔSBP was positively associated with ΔCr in the azilsartan group. In conclusion, there was no difference in the depressor effects of azilsartan and olmesartan, and there were no serious changes in biochemical parameters with azilsartan and olmesartan. (Int Heart J 2017; 58: 416-421) Key words: Blood pressure, Angiotensin II type 1 receptor blocker, Uric acid S even types of angiotensin II type 1 (AT 1 ) receptor blockers (ARBs) have been developed and are available for clinical use in Japan.1) ARBs is effective in the treatment of cardiovascular disorders, including hypertension and heart failure.1,2) ARBs have been reported to have class-specific (common) and moleculespecific (differential) effects in basic experimental studies. 3)We have proposed that small differences in the molecular structures of ARBs could lead to differences in their abilities to influence the AT 1 receptor. 3,4) Azilsartan is the newest ARB to be approved for clinical use in Japan, and has a significant blood pressure (BP)-lowering effect, although the next generation ARBs could be a significant breakthrough in the field of cardiovascular medicine. 5)Azilsartan medoxomil and azilsartan have been reported to have greater antihypertensive effects than other ARBs.6-9) Azilsartan has been shown to bind tightly to and dissociate slowly from AT 1 receptors.10) Therefore, we hypothesized that the depressor effect of azilsartan may be superior to those of other ARBs in patients with hypertension (HTN). In this study, we performed a changeover from their prior ARBs to azilsartan or olmesartan in patients with hypertension, and compared the efficacy and safety of azilsartan to those of olmesartan in a prospective randomized clinical trial. MethodsStudy design: Sixty-four hypertensive patients who were treated with ARBs except for azilsartan and olmesartan were enrolled. We applied a changeover of ARBs, where patients were prospectively and randomly switched from their prior ARBs, except for azilsartan and ...

High-dose telmisartan/HCTZ therapy was associated with a significant reduction in BP and helped patients achieve their target BP.

A single-pill fixed-dose combination therapy with irbesartan 100 mg/day and amlodipine 5 mg/day was superior to the combination of valsartan 80 mg/day and amlodipine 5 mg/day with respect to significant decreases in BP, serum UA and TG in patients with hypertension.