Nitric oxide (NO), which is synthesized from the guanidino nitrogen of l-arginine by nitric oxide synthase (NOS), plays an important role in many physiological and pathological processes. Most of the effects of NO are mediated by cyclic guanosine 3'5 monophosphate (cGMP), which is synthesized by soluble guanylate cyclase (sGC) and degraded by phosphodiesterases (PDEs). Although the NO/cGMP pathway has been extensively studied, remarkably little is known about the regulation of NO release. Furthermore, controversial studies have indicated that intervention of the sGC/cGMP pathway modulates the release of NO. The purpose of this study was to evaluate the hypothesis that drugs that affect the sGC/cGMP pathway may modulate NO release and, if so, is there a correlation between NO levels and blood pressure effect? To this end, we investigated the effects of the PDE 5 inhibitor zaprinast on mean arterial pressure (MAP), nitrite/nitrate levels and cGMP in normotensive male Sprague Dawley rats. The results of the current study indicated that zaprinast dose-dependently increased plasma cGMP levels at 18, 24 and 36 mg/kg and decreased MAP at 24 and 36 mg/kg. However, zaprinast at 18, 24 and 36 mg/kg did not affect NO levels either in serum or aortic tissue. We have concluded that the PDE 5 inhibitor zaprinast has no regulatory effect on NO release in serum and aortic tissue, and NO was not involved in the hypotensive effect of zaprinast.

Animals↗

PubMedDate not supplied

The effect of arginine-vasopressin and its analogues upon the endocochlear potential in the guinea pig.

The effect of arginine-vasopressin (AVP) and its analogues upon the endocochlear potential (EP) was examined in the guinea pig. AVP decreased the EP reversibly and dose-dependently like lysin-vasopressin (LVP). V1 antagonist failed to block the effect of AVP upon the EP. V2 agonist reversibly decreased the EP like AVP. The results suggest that V2 receptors mediate the action of vasopressin on the EP.

Action Potentials↗

PubMedDate not supplied

Influence of matrix size, vessel shape, vascular diameter, flow velocity, course of vessels on MR angiography.

Basic experiments were done to examine the influence of the extent of curve, direction of flow, vascular diameter, velocity of flow, and course of vessels on MR angiography. In the first experiment, two phantoms were constructed of vinyl tubing, a hairpin type and one with tubes bent to varying degrees. These phantoms were imaged in two matrices, different FOV, and of various velocities with a 1.5 Tesla system. Images of a normal volunteer were also obtained. In studies of the hairpin phantoms, a low intensity artifact appeared at the curve position, and the edge became fuzzy when the flow was perpendicular to the phase encoding direction. These phenomena were more apparent with a smaller matrix, smaller FOV, more gentle angle, larger diameter, and faster flow; in other words the component along the direction was dominant. In the phantom that used bent tubes, another low intensity artifact appeared on the medial side of the outflow portion. The results obtained from the volunteer corresponded well to those from the basic experiments. It was thought that the profile of flow was not well demonstrated due to the coarse matrix. In the second experiment, water flowed at various speeds through three-dimensional phantoms that were made of vinyl tubes of various diameters and directions. The phantoms were imaged with two- and three-dimensional time of flight and phase contrast angiography. The lower limits of detection of the phase contrast method were almost the same. In the coronal plane, the lower limit decreased to 2.5 mm for arteries and 9.5 mm for veins.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Flow Velocity↗

PubMedDate not supplied

Pharmacological studies on the hypoglycemic effect of 7,8-dihydro-2-(4-methylpiperazinyl)-4-(1-pyrrolidinyl)-6H-thi opyrano [3,2-d] pyrimidine dimaleate (MTP-1307), a novel hypoglycemic agent.

MTP-1307, 7,8-dihydro-2-(4-methylpiperazinyl)-4-(1-pyrrolidinyl)-6H- thiopyrano[3,2-d]pyrimidine dimaleate, is a novel oral hypoglycemic agent, structurally different from any existing hypoglycemic drugs. In fasted rats, the hypoglycemic effect of MTP-1307 was accompanied by elevation of the plasma insulin. In glucose tolerance tests, MTP-1307 suppressed the hyperglycemia after glucose loading and significantly enhanced the glucose-induced insulin secretion. In isolated hepatocytes from fasted rats, MTP-1307 inhibited gluconeogenesis from lactate and alanine. Furthermore, MTP-1307 increased the lactate/pyruvate ratio but did not increase the lactate level. MTP-1307 did not influence glycogenolysis in isolated hepatocytes from fed rats. In genetically diabetic ob/ob mice, MTP-1307 decreased the blood glucose level and improved glucose tolerance, but did not affect the level of plasma insulin. MTP-1307 increased 14CO2 production from glucose in isolated epididymal fat pads of ob/ob mice. Thus, these findings suggest that MTP-1307 produces hypoglycemic activities not only in normal animals but also in genetically diabetic animals, and that the hypoglycemic mechanism of MTP-1307 involves the promotion of glucose utilization in adipose tissue and, partially, the inhibition of gluconeogenesis in the liver and the stimulation of insulin release from the pancreas.

Adipose Tissue↗