WKY Animals Research Articles

Hypertrophy of arteriolar smooth muscle cells in the rat small intestine during maturation

The purpose of this study was to define structural characteristics for vascular smooth muscle (VSM) cells from the submucosal arteriolar system of the rat small intestine during maturation. Arterioles from 6- to 8-week-old and 10- to 12-week-old male WKY animals were selected from tissue prepared for scanning electron microscopy and mounted on end so that the entire circumference of each vessel could be observed by serial photography using scanning electron microscopy. From each vessel segment, the following measurements were made: (1) outer vessel diameter, (2) number of VSM cells occupying a length of vessel, (3) the number of resolutions each VSM cell makes around the vessel, (4) length of individual VSM cells, and (5) width of lateral processes along their length. At a given age, the length and width of the VSM cell was statistically similar for all types of arterioles. However, the VSM cell increased substantially in length and width from the 6–8- to 10–12-week time periods. The outer diameter for a particular arteriolar type also increased with age. These data suggest that the intestinal vasculature as a common population of smooth muscle cells at a given age in terms of their length, size, and process morphology for the various types of arterioles. Furthermore, maturation of the microvessels is associated with a uniform hypertrophy of the VSM cells from the majority of arterioles such that cells of young adult rats and those of juvenile animals represent distinctly different populations.

Blood pressure and plasma renin activity responses to chronic stress in the borderline hypertensive rat

The purpose of this study was to examine the systolic blood pressure and plasma renin activity (PRA) responses to chronic stress in normotensive rats and in rats with one hypertensive parent. Twenty-four male Wistar-Kyoto (WKR) and 24 male F 1 offspring of spontaneously hypertensive and WKY rats (BHR) were randomly assigned to 3 groups of 8 each. Experimental (E) animals were subjected to 2 hr daily of shock-shock conflict. Each response produced a 0.2 sec, 0.2–0.4 mA cutaneous electric shock. Failure to respond in 10 sec resulted in a train of 5 shocks (0.2 sec each sec). Yoked animals (Y) received the same shocks as E but had no control over their presentation. Finally, a control group (C) for maturation received no shocks. The E and Y animals were subjected to 14 weeks of conflict and were then monitored an additional 14 weeks in the absence of shock. All animals had their tail cuff blood pressures taken weekly except for 3 times when bloods were obtained for PRA assays. Analysis of blood pressure data revealed that: (1) BHR animals showed more of a blood pressure response to shock than WKY animals; (2) Y animals showed more of a response to conflict than E, especially for the BHR group; and (3) BHR shocked animals remained permanently elevated compared to BHR control animals even in the 14 week post-conflict period during which no shocks were given. Although PRAs for BHR animals were significantly higher than for WKY at the beginning of study, the stress-induced hypertension was associated with either normal or suppressed PRA values, suggesting that the hypertension in these animals is not a high renin hypertension.

Changes in paraventricular vasopressin and oxytocin during the development of spontaneous hypertension.

The potential role of central neuroendocrine changes in the development of spontaneous hypertension was evaluated. The developmental changes in blood pressure and hypothalamic and plasma levels of vasopressin (AVP) and oxytocin (OT) were determined in groups of SHR and WKY animals from 3 to 24 weeks of age. Hypothalamic OT content was significantly lower in 3-, 6-, and 12-week-old SHR rats compared to age-matched WKY animals. Hypothalamic AVP content was not different at 3 weeks of age, but was lower in the SHRs at 6 and 12 weeks. To localize strain differences in AVP and OT, specific hypothalamic nuclei were removed from 300 microns frozen brain sections, and hormone content measured. Paraventricular AVP and OT content was lower in the SHRs which had increased blood pressure (6, 12, and 24 weeks of age) but not in the prehypertensive groups (3 weeks of age). Neuropeptide content was unchanged in the supraoptic nucleus or median eminence. Plasma levels of AVP were increased in the SHR, while OT was unchanged. Thus, genetic hypertension is associated with specific and localized changes in hypothalamic AVP and OT. The fact that the peptide deficit occurred in the paraventricular nucleus, a region thought to be involved in the control of autonomic function, may have important implications in terms of the pathogenesis of hypertension.

Pituitary and Testicular Function in Spontaneously Hypertensive Rats

Levels of plasma gonadotropins, prolactin (PRL), and testosterone, and the testicular concentration, total content, and affinity of hCG binding sites were measured in male spontaneously hypertensive rats (SHR) and in genetically matched normotensive (WKY) rats. Hypertensive rats had higher plasma PRL and FSH levels and lower plasma testosterone levels. The affinity of testicular hCG binding sites was similar in SHR and WKY rats, but SHR had considerably lower concentration and total content of hCG-binding sites than did WKY animals. The comparison of these findings with those obtained previously with pituitary-grafted rats and with tumor-bearing rats indicates that the endocrine effects of hyperprolactinemia may vary depending on the rate and magnitude of the increase in peripheral PRL levels. Species differences in the response to hyperprolactinemia and differences between SHR and other rat strains suggest that hormonal responses to PRL elevation depend also on the genetic characteristics of the animal.

Dopamine β-hydroxylase: Determination of half-life and appearance in lymph fluid after IV injection of 125I-DBH into rats

A 4 day half-life of dopamine beta-hydroxylase (DBH) was determined for rats injected IV with 125I-rat DBH from the slow exponential component of radioactivity appearing in plasma, urine, feces and combined urine and feces. Half-life estimates for 125I-rat DBH injected IV into WKY and SHR animals did not differ from Sprague Dawley (Zivic Miller) rats. Radioactivity declined in parallel in plasma, urine and feces following IV 125I-rat DBH administration and each radioactivity falloff curve could be resolved into two components. The slow phase of the decline of radioactivity excreted into urine and feces from which DBH half-life was calculated occurred between 5 and 25 days after 125I-rat DBH injection. The early fast phase which is associated with distribution of the exogenous protein in body fluids and tissues continued for approximately the first 140 hr after DBH injection. The distribution characteristics of IV administered active bovine DBH and 125I-rat DBH into the lymphatic system were examined. After active bovine DBH or 125I-rat DBH was injected IV into rats, active DBH or radioactivity, respectively, appeared in lymph fluid (thoracic duct) within 20 min; reached peak concentrations within 90 min, and thereafter, declined in parallel with the plasma concentration. The concentration of radioactivity in plasma and lymph fluid were found to be unequal at 9 hr but were equivalent 68–75 hrs after IV injection of 125I-rat DBH. Based on the amount of active DBH or radioactivity which accumulates in lymph fluid it is clear that'a substantial amount (> 50%) of the DBH in blood circulates through the lymphatic channels. Analysis of parallel experiments with labelled serum albumin indicate that use of these methods to study plasma proteins do provide sensitive measures of biological half-life and lymphatic distribution characteristics. Specifically for DBH, the results of our study suggest that DBH normally circulates in plasma and lymph fluid with a biological half-life of 4 days.

Cardiovascular and sympathetic effects of l-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine in conscious SHR and WKY rats.

Injections of 1-)-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine (alkylacetyl-GPC, 0.2-5.0 nmol/300 g body weight) induced dose-related hypotension and tachycardia in spontaneous hypertensive (SHR) and normotensive control (WKY) rats. The hypotension that developed was more pronounced in SHR than in WKY rats and was unchanged by indomethacin pretreatment. Plasma norepinephrine (NE) and epinephrine (EPI) levels were markedly increased at the time of maximal hypotension (2 min after injection of alkylacetyl-GPC); plasma EPI (but not NE) was higher in the SHR than in WKY animals. Plasma levels of TXB2, but not 6-keto-PGF 1 alpha, increased in both groups; the increase was more pronounced in SHR than in WKY rats. In pithed SHR rats, alkylacetyl-GPC caused only short lasting hypotension without any effect on heart rate or circulating levels of NE or EPI. These data suggest that there is an increased vascular sensitivity to alkylacetyl-GPC in SHR rats and activation of thromboxane-generating elements in both SHR and WKY rats.

Angiotensin induction of active responses in cultured reaggregates of rat aortic smooth muscle cells.

Electrical activity was studied in cultured reaggregates of vascular smooth muscle cells prepared from the aortas of normotensive (WKY) and spontaneously hypertensive (SHR) rats. There were no significant differences between the resting membrane potentials of WKY (- 44.7 +/- 0.5 mV) and SHR (- 45.6 +/- 0.5 mV) reaggregates. Electrical field stimulation elicited active responses that consisted of two components: an initial spike component (amplitude, 30-40 mV; +Vmax 1-3 V/s) and a plateau component (amplitude, 10-30 mV; duration 3-5s; +Vmax, 0.1-0.3 V/s). Often the spike component was absent. Both components of the response were abolished by verapamil, Mn++, and Na+-free solutions indicating that Na+ and Ca++ currents may be associated with them. Addition of 10 mM TEA increased the duration of the response, and addition of 0.5 mM BaCl2 to the TEA solution increased the duration even further. The spike component always occurred in the presence of TEA and Ba++. No differences were observed between responses in WKY and SHR reaggregates. A bolus of angiotensin II (AII) (bolus concentration of 1 micro M) elicited a transient depolarization. In some cells an active membrane response was triggered by the depolarization and sometimes included the spike component. Replacing all the Na+ in the solution with either Tris or choline resulted in loss of the response to AII, and in some cells a hyperpolarization was actually seen on addition of the AII. The response to AII was insensitive to verapamil (up to 10(-5) M), but was blocked by 1 mM MnCl2. Reaggregates from both WKY and SHR animals gave similar responses to AII. The data indicates that cultured reaggregates of vascular smooth muscle are electrically excitable and are sensitive to angiotensin. Therefore functional angiotensin receptors must be present in the cultured cells.

Glucose oxidation in skeletal muscle from the spontaneously hypertensive rat

The metabolic activity of the cremaster muscle, as measured by glucose oxidation, was lower (16.7%) in the spontaneously hypertensive rat (SHR) than in the normotensive Wistar-Kyoto rat (WKY). This alteration in metabolic activity was accompanied by a reduction of the respiratory rate (12.5%) in the SHR rats when compared to WKY animals. The decreased respiratory rate and the lowered metabolic activity of the cremaster muscle occured at a time when blood pressure is increasing in SHR animals.