Captopril treatment and its withdrawal prevents impairment of endothelium-dependent responses in the spontaneously hypertensive rat.

Angiotensin converting enzyme inhibitors (ACE-I) have been shown to prevent impairment of endothelial cell function in Spontaneous Hypertensive rats (SHR). The purpose of this study was to examine the effects of early, long-term captopril (ACE-I) treatment and its withdrawal on vascular reactivity in SHR. Three groups of male SHR were studied: 1) untreated SHR; 2) SHR treated with captopril in-utero and maintained on oral treatment post-weaning (SHRCAP); and 3) SHR treated with captopril in-utero followed by withdrawal of drug therapy at two months of age (OFFCAP). All rats were studied at six months of age. Isolated aortic ring segments were suspended in tissue chambers for measurement of isometric force. Ring segments were exposed to cumulative concentrations of serotonin or phenylephrine (3 x 10(-9)-3 x 10(-5) M). SHR demonstrated an enhanced sensitivity to serotonin induced contraction. EC50 value were: SHR 3.6+/-1.4 x 10(-7)M, SHRCAP 9.5+/-0.5 x 10(-7) and OFFCAP 8.1+/-0.9 x 10(-7). Endothelium-dependent relaxation to acetylcholine (ACh) was markedly impaired in the SHR. Maximum relaxation (Rmax) to ACh was 61.1+/-1.6% of serotonin induced contraction versus 91.4 +/- 1.2% and 90.7 + 1.8% relaxation in SHRCAP and OFFCAP, respectfully (p<0.05). These data suggest that early, long-term treatment with captopril can prevent alterations in endothelial function observed in SHR even after ACE-inhibitor therapy has been stopped.

Neuropeptide Y (NPY) levels in alcoholic and food restricted male rats: implications for site selective function.

Neuropeptide Y (NPY) has been implicated in the control of ingestive, cardiovascular, and reproductive function. Blood pressure and sexual function were examined in Long-Evans rats receiving 6% ethanol-containing or calorically matched liquid diets, or rat chow ad lib. After 12 weeks of exposure, rats were sacrificed and plasma hormone levels and NPY content of microdissected brain regions were determined. Neither long-term alcohol ingestion nor caloric restriction were associated with major decrements in copulatory behavior. Long-term alcohol ingestion was associated with decrements in erectile function ex copula. Long-term alcohol ingestion was also associated with: (i) a moderate degree of hypertension; (ii) a failure to gain weight; (iii) decrements in circulating levels of LH, testosterone, and ACTH (but not progesterone); and (iv) increased corticosterone levels. Long-term alcohol ingesting and calorically-restricted rats exhibited alterations in daily feeding patterns. These physiological changes in response to long-term alcohol ingestion or caloric restriction were associated with neural site-selective differences in NPY content. Elevated NPY in the paraventricular nucleus was associated with voluntary (as in alcohol ingestion) or involuntary (as in caloric restriction) reductions in food intake. Differences in NPY in the suprachiasmatic and ventromedial nuclei were associated with the differences in feeding patterns. The decrements in hormone levels were associated with higher levels of NPY in the median eminence and in the arcuate nucleus.

Effects of angiotensin II on sexual function, blood pressure, and fluid intake are differentially affected by AT-1 receptor blockade.

We have previously reported that third ventricular administration of angiotensin II (ANG II) immediately before mating tests suppressed copulatory behavior in male rats. The present studies examine the effects of short- (3 days) and long-term (21 days) intracerebroventricular (i.c.v.) infusion of ANG II (6 microg/h), on parameters of copulatory behavior, fluid intake, and blood pressure in sexually experienced male Long Evans rats. Further, to test the hypothesis that suppression of masculine copulatory behavior by ANG II involves interaction with the angiotensin AT-1 receptor, a highly selective nonpeptide antagonist (L-158,809) was administered in the drinking water (25 mg/liter) to a group of ANG II-infused animals. I.c.v. infusion of ANG II was associated with increases in systolic blood pressure and fluid intake. In copulatory tests after 3, 9 and 15 days of infusion, rats infused with ANG II exhibited increased latencies to the initiation of copulatory behavior and to ejaculation, as well as increased intervals to reinitiate copulatory behavior after the ejaculation. Administration of L-158,809 blocked the effects of i.c.v. infusion of ANG II on systolic blood pressure and fluid intake. Further, L-158,809 attenuated the effects of i.c.v. infusion of ANG II on parameters of copulatory behavior. Data from this study provide support for a modulatory role for ANG II in the regulation of sexual behavior. In addition, this regulation seems to involve the AT-1 receptor.

Chronic ethanol ingestion alters parameters of mid-latency auditory evoked potentials in male rats.

The purpose of this study was to determine the effects of chronic ethanol ingestion on components of mid-latency auditory evoked potentials (MAEPs). Male Sprague-Dawley rats were administered 10% ethanol in drinking water for 10 months. MAEPs were obtained and compared to age-matched controls provided tap water. Data were obtained for varying frequencies (4, 8, 16, 24, and 32 kHz) and intensities (65, 75, and 85 dB sound pressure level). Ethanol treatment was associated with increased latencies, as well as decreased amplitudes of Na and Pa. The effects were most prominent for MAEP component Pa, but also appear for component Na. We suggest that chronic alcohol consumption induces structural and/or neurochemical alterations in substrates for cortical information processing.

Testosterone-induced copulatory behavior is affected by the postcastration interval.

A well entrenched hypothesis regarding hormonal action is that as the time interval following hormonal deprivation increases there is a corresponding decrease in the sensitivity of the system to the effects of hormone replacement. With this in mind, we examined the effects of a prolonged period of hormonal deprivation (9 mo), and compared these to the effects of a shorter period (1 month), on the restoration of copulatory behavior and seminal vesicle weights. Castration of sexually vigorous male Long-Evans rats at 6 mo of age was followed by the virtual disappearance of ejaculatory behavior within 1 mo. Testosterone (T) was administered (5 mm or 20 mm T-containing Silastic capsules) either 1 or 9 mo after castration, and copulatory tests were conducted 3, 7, 10, 14, and 17 days later. 5 mmT and 20 mmT were equally effective in restoring behavior in the rats treated 1 mo after castration. In contrast, 5 mmT was more effective in inducing copulatory behavior than 20 mmT in the rats treated 9 mo after castration. The time course to maximal effect was longer in the rats given T 9 mo after castration. Rats were sacrificed 21 days after T administration. Expressed seminal vesicle weights and plasma testosterone were increased in a dose-dependent manner independent of the postcastration interval. These data indicate that somatic and behavioral effects of T are differentially modified by the period of preceding hormonal deprivation.