Agnes E. Jimenez

Separate hemodynamic roles for chloride and sodium in deoxycorticosterone acetate-salt hypertension.

Abstract It has been reported that both sodium and chloride ions must be injested to induce the elevated blood pressure of deoxycorticosterone acetate (DOCA)-salt-sensitive hypertension. This study was designed to determine the separate roles of the sodium and chloride ions in the altered hemodynamics underlying the high blood pressure. DOCA pellets (75 mg) were implanted in uninephrectomized rats and the animals were then fed one of four diets: (i) high sodium chloride, (ii) high sodium-low chloride, (iii) high chloride-low sodium, or (iv) low sodium chloride. Blood pressures were measured weekly by tail-cuff plethysmography for 5 weeks and the animals were then subjected to a terminal experiment to measure cardiac output by thermodilution technique, renal blood flow by electromagnetic flow probe, and direct arterial pressure. Blood pressure in the DOCA-high NaCl group was significantly greater (P<0.05) compared with that of the DOCA-low NaCl group (160 ± 3 mm Hg vs 124 ± 2 mm Hg, respectively) at 5 weeks after treatment; all other groups were not significantly different from the DOCA-low NaCl group. Cardiac output was significantly greater in DOCA-treated rats consuming diets high in sodium (44 ± 2 ml/min/100 g) or sodium chloride (40 ± 2 ml/min/100 g) compared with animals consuming low sodium chloride (31 ± 2 ml/min/100 g; P < 0.01 for each comparison). Direct intraarterial blood pressure and renal blood flow were used to calculate renal vascular resistance. Renal vascular resistance was increased in those DOCA-treated rats consuming diets high in chloride (42 ± 3 mm Hg/ml/min/100 g) and high sodium chloride (54 ± 3 mm Hg/ml/min/100 g) compared with rats consuming low sodium chloride (30 ± 3 mm Hg/ml/min/100 g; P < 0.01 for each). It appears that elevations in cardiac output are associated with increased dietary sodium and act in synergy with the elevations in renal vascular resistance associated with increased dietary chloride. Increases in both cardiac output and renal vascular resistance are involved in the maintenance of elevated blood pressure in the DOCA-salt-sensitive model of hypertension.

Effect of Human Chorionic Gonadotropin on Reproductive Organ Blood Flow in Cycling Rats

Abstract Recent characterization of luteinizing hormone (LH)/human chorionic gonadotropin (hCG) receptors in uterine vascular tissue, evidence that expression of these receptors is cyclic in nature, and demonstration of a correlation between hCG level and uterine vascular resistance lead us to investigate the effect of hCG administration on blood flow in reproductive organs of cycling and ovariectomized Sprague-Dawley rats. Blood flow (ml/min/g dry wt/cardiac output ± SEM) was determined by microsphere spectroscopy (57Co, 113Sn, 95Nb, 141Ce). Baseline uterine (0.5842 ± 0.1037) and cervical (0.7785 ± 0.1199) blood flows were greater in diestrus-2 rats than in every other group. Diestrus-2 (0.4530 ± 0.0584) and estrus (0.4692 ± 0.0848) rats had greater baseline ovarian blood flow than proestrus rats (0.2521 ± 0.0279). A single intraperitoneal injection of 50 IU hCG on each day of the 4-day estrus cycle decreased uterine flow by more than 30% within 20 min (P < 0.05), but did not alter uterine flow in ovariectomized rats. This dose of hCG also decreased ovarian flow in diestrus-2 rats (0.5219 ± 0.0857 to 0.4207 ± 0.0753), decreased liver flow in diestrus-2 (0.0282 ± 0.0060 to 0.0231 ± 0.0051) and estrus (0.0301 ± 0.0029 to 0.0203 ± 0.0038) rats, and increased liver flow in ovariectomized rats (0.0279 ± 0.0054 to 0.0325 ± 0.0050). Injection of 0.10 IU hCG did not alter blood flow to reproductive organs in any group, but decreased liver flow in estrus rats (0.0469 ± 0.0121 to 0.0326 ± 0.0088). Neither dose of hCG altered cervical, kidney, or skeletal muscle flow in any group. Our results indicate an organ specific, dose-dependent blood flow response to hCG in cycling rats, which appears, in the case of uterine flow, to be attenuated by removal of the ovaries. The present findings suggest high doses of hCG given clinically may decrease uterine flow and potentially lead to implantation failure. [P.S.E.B.M. 1996, Vol 211]

Developmental Patterns of Tyrosine Hydroxylase Activity in Discrete Central Nervous System Regions and Serum LH and Prolactin in the Prepubertal Rat

Changes in tyrosine hydroxylase (TH) activity in the whole hypothalamus and discrete nuclear regions of the limbic system were observed to occur from 10 to 40 days of age in the female rat. In the whole hypothalamus, TH activity increased between 10 and 30 days of age then decreased at 40 days of age. In the preoptic (POA) and suprachiasmatic nuclear areas (SCN), TH activity increased to peak values at 20 days then declined to baseline values at 25 days. However, an increase in TH activity of SCN was again noted at 39 days of age. TH activity in the amygdala area (AMYG) increased to peak values at 25 and 30 days with a return to baseline levels at 35 days, while in the median eminence (ME), TH activity increased at 20 days and remained elevated through 39 days of age. These results show that temporally distinct changes in TH activity occur during development in various areas of the brain. These changes may represent maturation of neuronal control systems known to be involved in adult reproductive function. Serum LH levels in the developing rat increased between days 10 and 25 then showed a precipitous drop at day 30 followed by increased values at days 35-39. Serum prolactin levels remained low through day 20, increased at days 25-30 then decreased on day 35 with a peak at day 37, prior to the onset of puberty. The inverse relationship of LH and prolactin at day 30 suggests a transient inhibitory (antigonadotropin) effect of increasing prolactin levels on LH at this time.(ABSTRACT TRUNCATED AT 250 WORDS)

Uptake of serotonin and norepinephrine in hypothalamic and limbic brain regions during the estrous cycle and the effect of neurotoxin lesions on estrous cyclicity

The temporal pattern of hypothalamic and limbic aminergic activity during the estrous cycle has been measured by changes in the serotonergic and noradrenergic neuronal uptake during the regular estrous cycle. Significant changes (p = 0.006, 0.01) in the uptake of 3H 5-HT and 3H NE were recorded in the suprachiasmatic nuclei (SCN) at 1200 hours on proestrus. Significant changes (p = 0.01, 0.018) in the uptake of 3H 5-HT in the preoptic area (POA) were found at 1200 hours on both diestrus and proestrus while median eminence (ME) 5-HT showed a significant increase only during proestrus (p = 0.001). In the amygdala (AMYG) 3H 5-HT uptake was significantly different at 1200 hours on diestrus and proestrus while 3H NE uptake was significant (p = 0.001) at 1200 hours only during proestrus. The plasma proestrous luteinizing hormone surge occurred at 1700 hours. The serotonin neurotoxin, 5,7-dihydroxytryptamine, was stereotaxically injected through a 30 gauge needle in concentrations of 5-10 micrograms/microliters/minute for 1 minute in various nuclear regions. In the SCN 4 or 5 day estrous cyclicity was interrupted by diestrus for average periods of up to 15 days; in the POA for periods of 10 days; in the ME for periods of 13 days; and in the AMYG for periods of up to 6 days. Sham injections of 5% ascorbic acid had no effect on cyclicity and following these periods of acyclicity rats resumed normal cycles. These lesion effects and patterns of uptake suggest a common timing mechanism utilizing serotonergic raphe systems for neuroendocrine control. Lesions with 5,7-DHT in all four brain regions disrupt cyclicity, but the greatest delays occur in the SCN and ME regions which are particularly critical to intrinsic neuroendocrine rhythms. Patterns of increase in reuptake capacity in all 4 regions occur 3 hours prior to the critical period for the plasma LH surge and may be an important mechanism for many types of neuroendocrine events including ovulation.

Plasma Luteinizing Hormone and Prolactin Levels and Hypothalamic Catecholamine Synthesis in Steroid-Treated Ovariectomized Rats

The effects of estrogen (E) and progesterone (P) on synthesis rates and endogenous levels of hypothalamic norepinephrine (NE) and dopamine (DA) were determined in individual ovariectomized (OVX) rats. 3H-tyrosine (3H-T) was injected intra-arterially and the rate of its incorporation into 3H-DA and 3H-NE was determined at 10, 15, 30, and 45 min. Steroid treatment for 2 days effectively decreased plasma LH levels and elevated plasma prolactin (Prl) levels while endogenous levels of NE and DA were not affected. NE synthesis was not affected by steroid treatment. A significant increase in DA synthesis was correlated with low plasma LH levels, suggesting that DA inhibits LH release. The elevated plasma Prl levels seen in steroid-treated rats were correlated with increased DA synthesis in the hypothalamus. This may indicate that elevated plasma Prl levels stimulate dopaminergic neurons in a short-loop negative feedback fashion.

Predisposition to Hypertension in Rat Pups from Renal Hypertensive Dams

We determined that a predisposition to hypertension could be transmitted by a nongenetic, renal hypertensive (HT) mother to her pups. The pups of one-kidney: one clip Goldblatt (1K:1C) hypertensive female rats and of sham operated normotensive female rats were subjected to the 1K:1C procedure at 28 days of age and tail cuff blood pressures (BP) were determined. After surgical induction of hypertension, HT male pups of HT dams had a significantly greater (p less than .05) BP by 14 days after surgery (194 +/- 8 mm Hg) than did HT male pups of normotensive (NT) dams (169 +/- 6 mm Hg). A similar trend (p less than .08) was observed for the HT female pups of HT dams (185 +/- 7 mm Hg) compared to HT females from NT dams (163 +/- 4 mm Hg). Thus, in utero exposure of pups to a chronic HT state alters the response of the pups to the surgical induction of hypertension. Furthermore, the results suggest that transfer of a predisposition to hypertension from mother to offspring occurred during the pregnancy/lactation period.

Circadian patterns of serotonin (5-HT) accumulation after pargyline treatment in the rat hypothalamus during development

The purpose of this study was to determine if developmental changes in serotonin (5‐HT) synthesis occur during maturation of the 5‐HT circadian rhythm in the rat hypothalamus of 10‐ to 35‐day‐old rats. Pargyline (75 mg/kg, s.c.), a monoamine oxidase (MAO) inhibitor, was administered 30 min prior to decapitation. Hypothalamic 5‐HT concentrations after pargyline treatment were measured at six time points over a 24‐hr interval in male and female rat pups at 10, 20, 30 and 35 days of age.

Cardiac output and the blood pressure increase in deoxycorticosterone acetate-salt hypertension after nicotine infusion.

We wished to determine if nicotine exaggerates the blood pressure increase in deoxycorticosterone (DOCA)-salt hypertension. Uninephrectomized, male Sprague-Dawley rats were implanted with DOCA pellets (75 mg) and placed on a 5.2% salt diet for sixteen days and then infused with nicotine (DOCA-Nicotine; 2.4 mg/kg/day) or vehicle (DOCA-Sham). Control animals were treated with vehicle (Control) or nicotine (Control-Nicotine). The DOCA-Nicotine group had significantly greater tail-cuff blood pressures than the DOCA-Sham group by one week of nicotine infusion. At 2.5 weeks of nicotine infusion the DOCA-Nicotine rats had significantly greater tail-cuff blood pressures, direct arterial blood pressures, and cardiac outputs compared to the DOCA-Sham animals. Renal blood flows were similar in the two groups. Control-Nicotine animals demonstrated no response to nicotine during 2.5 weeks of infusion. We conclude that in the DOCA-salt rat nicotine induces an exaggerated rise in blood pressure and that the mechanism involves an increase in cardiac output.

Kidney Blood Flow Changes in Shock

The syndrome of multiple-system organ failure (MSOF) was originally suggested by Baue [1] to be the sequential failure of two or more organ systems in critically ill patients. These initial patients were ill from diverse causes such as pancreatitis, heart disease and a leaking colon anastomosis. This orig inal observation was later confirmed and placed in to better focus by Eiseman [2] and Fry [3] where systemic infection was the identified common ethiologic thread. Although these reports devel oped mostly following multiple trauma, MSOF is currently recognized in a multitude of scenarios such as volume or cardiogenic shock, systemic in fection or the persistent foci of dead tissue. Invasive infection from an identifiable source need not be present for the development of the syndrome, but clearly the circulatory and hypermetabolic state commonly identified in sepsis is a constant feature of MSOF, implying activation of the inflammation cascade as an etiologic factor.

Cardiovascular Correlates of Predisposition to Hypertension in Pups of one Kidney: One Clip Renal Hypertensive Dams

We reported that the pups of one kidney:one-clip Goldblatt hypertensive (HT) rats have a predisposition to the induction of experimental hypertension. To investigate the nature of the predisposition, pups of HT dams were challenged with vasopressor agents at 28-days-of-age or treated with DOCA and 6.5% salt diet between 35 and 81 days-of-age. Pups of HT dams had a significantly greater blood pressure between 28 and 81 days-of-age and also showed a greater change in blood pressure when provided a 6.5% salt diet than did pups of normotensive dams. Pups of HT dams demonstrated a decreased bradycardic response after injection of angiotensin II (p less than .05) and a lesser change in mean arterial blood pressure after injection of angiotensin II or norepinephrine than did the pups from normotensive dams. These results suggest an effect of maternal hypertension on the development of cardiovascular control mechanisms in her offspring. The decreased pressor response suggests the predisposition is not due to an increased vascular sensitivity to vasopressors.