Effects of dietary protein on food and water intake in spontaneously hypertensive rats.

We have been studying the development of hypertension in spontaneously hypertensive rats (SHR) fed a low protein diet. The effects of a low protein diet upon food and water intake were examined. Body weight gain, food and water intake were measured in three to twenty-three week-old SHR and Wistar Kyoto rats (WKY) fed diets containing 8%, 15% or 25% casein. Body weights of SHR and WKY fed an 8% casein diet were significantly lower at 23 weeks than rats on the higher protein diets, although both groups on the 8% diet consumed more food and water per g of body weight. In addition, SHR fed an 8% casein diet drank less water per gram of food than WKY or SHR fed 15% and 25% casein diets. These results indicate that changes in food and water intake, as a consequence of low protein diets, should be an additional consideration when examining the effects of dietary protein on the development of hypertension.

Noradrenergic transmission in the isolated portal vein of the spontaneously hypertensive rat.

The effect of electrical field stimulation (1, 2, 5, 10 Hz for a total of 480 pulses at 15-minute intervals) on the release of 3H-norepinephrine from the superfused portal vein of spontaneously hypertensive rats (SHR) or Wistar-Kyoto rats (WKY) of various ages was studied. The ages of the animals were (in weeks) 5-6 (prehypertensive), 8-10 (young hypertensives), 16-18 (older hypertensives), and 28 (mature hypertensives). There was no difference in the release of 3H-norepinephrine or developed tension of the portal vein to any frequency of field stimulation of SHR or WKY at 5-6 weeks of age. However, there was a significantly greater release of 3H-norepinephrine and developed tension of veins of SHR in response to low (1 or 2 Hz) but not high frequencies (5 or 10 Hz) at 8-10, 16-18, and 28 weeks of age. Vessels from hypertensive animals also developed greater resting tension and spontaneous activity, which was reduced to that of WKY in the presence of an alpha-adrenergic antagonist. The alpha 2 selective adrenergic antagonist yohimbine produced the same degree of enhancement of release of 3H-norepinephrine to field stimulation of veins obtained from both SHR and WKY at 5-6, 8-10 and 16-18 weeks of age. However, the facilitory effect of yohimbine was significantly attenuated in portal veins obtained from SHR at 28 weeks of age compared to age-matched WKY.(ABSTRACT TRUNCATED AT 250 WORDS)

[Inhibitory effect of noradrenaline on dopamine release from the hypothalamus of the rat]. / Effet inhibiteur de la noradrénaline sur la libération de la dopamine par l'hypothalamus du rat.

1. The release of dopamine from the anterior hypothalamic/preoptic region of the anesthetized and artificially ventilated rats was investigated in vivo using a superfusion technique with a push-pull cannula. L-DOPA and pargyline were added to synthetic cerebrospinal fluid superfusing the area. Dopamine was measured by electrochemical detection after separation by liquid chromatography. Dopamine release rapidly reached stable values after the addition of L-DOPA. 2. Serotonin (10-6M) slightly inhibited dopamine release. Other experiments are necessary to characterize this interaction. 3. Lesions of the ventral noradrenergic bundle by a knife cut significantly increased the release of dopamine. 4. This lesion prolonged the apparent half-life of noradrenaline in the AH/PO. 5. Low concentration (10-7M) of noradrenaline inhibited dopamine release when a lesion was performed prior to the superfusion. 6. These data are compatible with a tonic noradrenergic mechanism mediating an inhibitory control of dopamine release in the AH/PO.

[Implication of anterior hypothalamic dopamine in the regulation of arterial pressure]. / Implication de la dopamine de l'hypothalamus antérieur dans la régulation de la pression artérielle.

The anterior hypothalamus is essential for the normal carotid sinus baroreceptor reflex. The dopamine innervation to this region is a projection from the dopaminergic A 14 cell group of the rostral hypothalamus. The anterior hypothalamic/preoptic region (AH/PO) was unilaterally superfused with buffer containing L-DOPA (10(-4) M) and the superfusate analyzed for dopamine using liquid chromatography with electrochemical detection. A stable release of dopamine was analyzed for dopamine using liquid chromatography with electrochemical detection. A stable release of dopamine was obtained within one hour. When the baroreceptor reflex loop was activated, a concomitant increase in dopamine release was observed. Lesions of the ventral noradrenergic bundle by a knife cut significantly increased the release of dopamine for at least two hours. The data are compatible with a tonic noradrenergic mechanism mediating an inhibitory control of dopamine release in the AH/PO. This dopaminergic involvement may play a functional role in blood pressure control.

In vivo dopamine release from the anterior hypothalamus of the rat.

The release of dopamine from the anterior hypothalamic/preoptic region of the anesthetized rat was investigated in vivo using a superfusion technique with a push-pull cannula. Dopamine was measured electrochemically after separation by liquid chromatography. The spontaneous release of dopamine was very low but detectable in some experiments. An inhibitor of monoamine oxidase (pargyline) and the immediate precursor of dopamine (L-DOPA) were added to synthetic cerebrospinal fluid superfusing the area. When these substances were present dopamine release was increased considerably and appeared to be stable for a long period of time. Mechanisms contributing to the formation of newly synthetized dopamine are discussed in relation to the releasing effect of d-amphetamine and the inhibiting effect of calcium-free medium. The functional significance of dopamine release was shown by the increased release of dopamine following an increase in blood pressure obtained by an intraarterial injection of blood. Finally, ventral noradrenergic bundle lesion on the same side of the superfusion site considerably enhanced dopamine release which may indicate an inhibitory control of dopamine release by noradrenergic neurons. Furthermore, this experimental procedure provides valuable means for analyzing the effects of pharmacological as well as other manipulations on the dopamine released from a superfused brain area in vivo.

A cannabinoid with cardiovascular activity but no overt behavioral effects.

Abnormal-delta8-tetrahydrocannabinol (ABN-delta8-THC) failed to elicit central nervous system and cardiovascular effects in laboratory animals. Abnormal-cannabidiol (ABN-CBD) was also devoid of overt behavioral effects but produced marked hypotension with only slight bradycardia in anesthesized dogs.

A potent antinociceptive cannabinoid which lacks opiate substitution properties in monkeys.

(-)-9-Nor-9beta-hydroxy-hexahydrocannabinol[(-)-9-nor-9beta-OH-HHC] produced hypotension and bradycardia in anesthetized dogs, was a potent antinociceptive agent in the mouse tail-flick and p-phenylquinone abdominal-stretching tests, but did not reverse the effects of morphine withdrawal in dependent monkeys.

Vasoconstrictor actions of delta8- and delta9-tetrahydrocannabinol in the rat.

Cardiovascular effects of delta8- and delta9-tetrahydrocannabinol (THC) were studied after systemic intravenous administration and intra-arterial administration into a perfused vascular bed in the urethane-anesthetized rat. Intravenous administration of delta8- and delta9-THC produced dose-related transient increases in blood pressure followed by more prolonged hypotensive responses and bradycardia. Intra-arterial administration of delta8- and delta9-THC into the perfused hindquarters of the rat produced an increase in perfusion pressure indicative of vasoconstriction. The vasoconstrictor response to the cannabinoids corresponded temporally to a similar response produced by i.a. norepinephrine and was in contrast to the more prolonged vasoconstrictor responses produced by vasopressin. Phentolamine, in a dose which reduced the vasoconstrictor effect of norepinephrine by 90%, significantly reduced the response to i.a. delta9-THC while having no effect on the actions of i.a. vasopressin. It was demonstrated that reserpine pretreatment significantly reduced vasoconstrictor actions of i.a. tyramine and delta9-THC but did not alter the responses to norepinephrine. These data suggest that delta8- and delta9-THC have peripheral vasoconstrictor activity in the rat which may be mediated, in part, through a tyramine-like action on adrenergic nerve terminals.

Tolerance to the cardiovascular effects of delta9-tetrahydrocannabinol in the rat.

1. Daily intraperitoneal injections of delta9-tetrahydrocannabinol (delta9-THC, 10 mg/kg) resulted in tolerance to the effects of the cannabinoid on body weight and body temperature within 1-2 weeks of treatment. 2. Tolerance failed to develop to the suppression of spontaneous motor activity produced by delta9-THC during 28 days of treatment with the cannabinoid (10 mg/kg, i.p. per day). 3. Following treatment with vehicle for 28 days, intravenous administration of delta9-THC in anaesthetized rats produced a transient pressor response followed by a sustained hypotension and bradycardia. 4. Tolerance to the hypotensive and negative chronotropic responses to intravenous delta9-THC was readily apparent in animals which had received daily intraperitoneal injections of delta9-THC (10 mg/kg) for 28 days. 5. Tolerance failed to develop to the pressor actions of intravenous delta9-THC after 28 days of preptreatment. 6. There was no difference in the pressor response to intravenous noradrenaline in vehicle-treated animals (1.0 ml/kg, i.p., per day for 28 days) and delta9-THC-treated animals (10 mg/kg, i.p., per day for 28 days).