Injection of L-allylglycine into the posterior hypothalamus in rats causes decreases in local GABA which correlate with increases in heart rate.

Injection of the GABA antagonist, bicuculline methiodide into the posterior hypothalamus of rats has been shown to cause marked increases in heart rate and lesser elevations in blood pressure. Allylglycine is a potent inhibitor of the synthetic enzyme for GABA, glutamic acid decarboxylase, only after in vivo biotransformation into its active form, 2-keto-4-pentenoic acid, through a stereospecific amino acid oxidase. The posterior hypothalamus is thought to contain substantial activity only of L-amino acid oxidase. In this study, the stereoisomers of allylglycine were injected into the posterior hypothalamus at a site also shown to be reactive to bicuculline. Injection of L-allylglycine but not D-allylglycine caused substantial increases in heart rate but only slight increases in blood pressure. Injection of the GABA agonist muscimol prior to treatment with L-allylglycine prevented these cardiovascular changes. In another series of experiments, levels of GABA in the posterior hypothalamus and adjacent areas were measured 90 min after unilateral injection of L-allylglycine (12.5 or 25 micrograms), D-allylglycine (25 micrograms) or saline into the posterior hypothalamus. Only L-allylglycine caused increases in heart rate and blood pressure and decreases in levels of GABA. Quantitatively, the increases in heart rate at sacrifice were strongly correlated with the decreases in levels of GABA in the injected posterior hypothalamus (r = -0.94; P less than 0.002) but not in other regions.(ABSTRACT TRUNCATED AT 250 WORDS)

Microinjection of GABA antagonists into posterior hypothalamus elevates heart rate in anesthetized rats.

Microinjection of the GABA antagonist bicuculline methiodide 1-25 ng into the posterior hypothalamus of urethane-anesthetized rats evoked sympathetically-mediated increases in heart rate of up to 150 beats/min and modest increases in blood pressure which could be prevented by prior local microinjection of muscimol 50 ng. Microinjection of picrotoxin but not strychnine produced similar effects. These results suggest that a latent sympathoexcitatory mechanism in this region is tonically inhibited by endogenous GABA.

Early microvascular pathology during hyperglycemia in bats.

The microvascular changes in the wing of bats, Myoitis lucifugus, were observed during 3 weeks of normal life and 5 weeks of streptozotocin induced hyperglycemia (300-400 mg/dl, plasma). During normal life, week-to-week variations in diameter and blood flow in the same set of vessels were minor. After hyperglycemia was induced, the major initial response was dilation of all microvessels except the smallest arterioles which constricted. The dilation phase was followed by progressive constriction of all vessels. Blood flow was near normal during the dilation phase, but flow gradually decreased as hyperglycemia continued and vasoconstriction occurred. The ability to repeatedly observe the same set of microvessels on a week-to-week basis and the absence of anesthesia may make the diabetic bat a useful model in which to study the early phases of microvascular pathology during chronic hyperglycemia, which begins abruptly in adult life. In addition, the sequence of microvascular changes during chronic hyperglycemia in the bat are qualitatively similar to those in other diabetic mammals, including man.

Early arteriolar and capillary changes in streptozotocin-induced diabetic rats and intraperitoneal hyperglycaemic rats.

Comparison of intestinal arteriolar characteristics in vivo were made in normal rats, normal rats injected intraperitoneally twice daily with either 0.15 mmol/l saline or 16.6 mmol/l glucose in 0.15 mmol/l saline (total value 5% of body weight), and in streptozotocin treated rats (plasma glucose greater than 22.2 mmol/l). Each regimen was continued for 4-5 weeks before the study. Interperitoneal injection of glucose increased the plasma glucose concentration by 0.8-1.6 mmol/l for 2-2.5 h. The microvascular characteristics of normal and saline injected rats were identical. Results obtained in glucose-treated and diabetic animals were very similar and included: 1) resting arteriolar vasodilation, 2) subnormal dilation at removal of all vascular control with adenosine, 3) total arteriolar vessel wall, including smooth muscle, cross-sectional area and wall to lumen ratio one-third to one-half less than normal, and 4) capillary separation distances increased above normal by 40%-50%. The results indicate that the morphological and functional changes in intestinal arterioles and capillaries found in diabetic rats after 4-5 weeks can be reproduced in the intestinal tissues of a normal animal exposed to intermittent increases in intraperitoneal glucose concentration.