Paul F. Rogers

Plasma catecholamines and neuropeptide-Y as indices of sympathetic nerve activity in normotensive and stroke-prone spontaneously hypertensive rats.

The suitability of plasma catecholamines (CAs) and neuropeptide-Y (NPY) as biochemical indices of sympathetic nerve activity (SNA) has been investigated, and these parameters have been compared between adult normotensive (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). Plasma norepinephrine (NE), epinephrine (E) and NPY were measured in venous and arterial blood samples taken from conscious, unrestrained rats. Under resting conditions, both CAs were significantly higher in SHRSP than in WKY; plasma E in particular was raised threefold. SHRSP had higher plasma levels of NPY in arterial blood but not in venous blood. Acute hydralazine-induced hypotension caused a slight rise in NPY and striking increases of CAs, which were accentuated in SHRSP. Ganglion blockade with pentolinium reversed these increases but the differences in basal plasma CA levels between strains still persisted. Barbiturate anaesthesia had little effect on plasma levels of NPY or NE, but plasma E levels were depressed, particularly in SHRSP, so that the strain difference in plasma E taken from venous blood was no longer apparent.

Influence of dietary sodium on blood pressure in baroreceptor-denervated rats.

One possible explanation for the salt sensitivity of blood pressure (BP) in certain hypertensive individuals is that neural mechanisms which normally counteract the pressor effect of a high dietary sodium intake are defective. We have tested this possibility in normotensive Wistar-Kyoto rats (WKY) by surgically ablating the arterial baroreflex mechanism. This manoeuvre, by itself, conferred substantial salt-sensitivity on the WKY rats whose BP is normally relatively insensitive to dietary sodium intake. The treated rats responded to a high sodium diet with a significant rise in systolic BP which was reversed by substituting a low sodium diet. Thus, impaired baroreflex function which has been observed in essential hypertension and in hypertensive animals, may be responsible for the hypertensive effect of sodium.

Effects of dietary sodium and fish oil on blood pressure development in stroke-prone spontaneously hypertensive rats.

The postulated antihypertensive effect of dietary fish oil and the influence of dietary sodium on this effect were evaluated in young stroke-prone spontaneously hypertensive rats (SHRSP) by direct intra-arterial measurement of blood pressure. Weaning rats were fed synthetic diets containing olive oil or eicosapentaenoic acid-enriched fish oil (5% of dry weight) with normal (0.23%) or high (2.8%) sodium content. Catheters were implanted after 3 months for blood pressure measurement under resting conditions and to sample blood for catecholamine determinations. Effects of fish oil on vascular reactivity were assessed in the in situ blood-perfused mesentery. The overall observation, from a series of experiments, was that feeding diets containing 5% fish oil to young SHRSP resulted in a small but consistent suppression of the development of hypertension. This effect could be counteracted, however, by increasing dietary sodium intake. Observations after ganglion blockade indicate that the antihypertensive effect of fish oil is unlikely to result from a reduction in sympathetic vascular tone.

Effects of chronic alcohol consumption and alcohol withdrawal on blood pressure in stroke-prone spontaneously hypertensive rats.

The development of blood pressure was monitored by the tail-cuff method in normotensive (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) receiving ethanol (alcohol) in drinking water from weaning (approximately 1 month of age). Alcohol administration over a 3-month period attenuated the development of hypertension in SHRSP and also caused a small reduction of the initial blood pressure rise in WKY. This was accompanied by a reduction of fluid intake and an increase of circulating antidiuretic hormone (arginine vasopressin; AVP). Circulatory volume remained constant. Direct measurement of arterial blood pressure in conscious rats before and after autonomic blockade confirmed the antihypertensive effect of alcohol in SHRSP and indicated that it is at least partly dependent on altered activity of neural mechanisms. Sudden withdrawal of alcohol caused an immediate increase of fluid intake followed by a rise of blood pressure lasting several days in both WKY and SHRSP. This withdrawal hypertension could not be attributed to changes in plasma catecholamines or AVP.

Blood pressure reduction by fish oil in adult rats with established hypertension — Dependence on sodium intake

The effects of fish oil combined with dietary sodium restriction on blood pressure and mesenteric vascular resistance were examined in a series of experiments with adult normotensive (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). Rats were fed normal or low sodium diets containing fish oil, olive oil or safflower oil. Small but significant reductions of blood pressure (measured directly in conscious rats) were seen in SHRSP but not in WKY after 8 weeks on a fish oil/low sodium diet, compared with rats fed olive or safflower oil diets with normal sodium content. This antihypertensive effect was not dependent on neurally mediated vasoconstriction but was associated with a reduction of basal resistance in the blood-perfused mesenteric artery. Subcutaneous injection of fish oil reduced blood pressure in adult SHRSP on a normal sodium diet. However, there was a further fall in blood pressure when sodium intake was reduced. The results indicate the antihypertensive effect of fish oil can be enhanced by restricting sodium intake.

Antihypertensive effect of alcohol in spontaneously hypertensive rats.

The influence of ethanol (alcohol) consumption on blood pressure during and after the development of hypertension was examined by using spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP). Normotensive Wistar-Kyoto (WKY) rats were also used for comparison. Substituting alcohol (5–20%) for drinking water at 1 month of age retarded the age-dependent rise of blood pressure hi all three strains so that, at 7 months, blood pressure measured by a tail-cuff method was 24 mm Hg, 26 mm Hg, and 41 mm Hg lower in the alcohol-treated WKY rats, SHR, and SHRSP, respectively, than in untreated rats. Significant differences in blood pressure were seen in each strain after only 3 months. Withdrawal of alcohol at this stage caused an acute rise of blood pressure then a return to subnormal levels, which persisted for a further 3 months. Administration of 15% alcohol to adult WKY rats and SHR for 2 months had no significant effect on blood pressure. Increasing alcohol content to 20% for a further 2 months prevented rises of blood pressure hi both strains. Thus, although continuous drinking of alcohol does not lower blood pressure, it appears to counteract the development of hypertension in rats.

Limited baroreflex control of heart rate in young stroke-prone spontaneously hypertensive rats

Controversy regarding possible differences of baroreflex gain in spontaneously hypertensive rats (SHR) and their relationship to the rise in blood pressure may be due in part to variations in the methods used to assess baroreflex function. In this study, we have compared the baroreflex control of heart rate in normotensive (Wistar-Kyoto, WKY) and stroke-prone spontaneously hypertensive (SHRSP) rats at 1 and at 7 months of age. Mean arterial pressure and heart rate were monitored in conscious rats following implantation of arterial and venous catheters. Phenylephrine and nitroprusside were given intravenously and the peak responses of mean arterial pressure and heart rate were recorded. In the young rats, these recordings were repeated under anaesthesia. Individual slopes for responses to phenylephrine or nitroprusside were obtained by linear regression. A single relationship covering both sets of responses was also obtained by fitting the data to a sigmoidal curve. The latter approach enabled the baroreflex to be represented as a single function which has a single determinant of gain, operates within defined limits and can be readily related to resting mean arterial pressure and heart rate. This approach demonstrated that: (1) in adult SHRSP, the baroreflex had reset to operate at higher resting levels of mean arterial pressure; (2) the range of heart rate control was smaller in both young and adult SHRSP compared with WKY; (3) average gain was slightly, but not significantly lower in adult SHRSP; (4) anaesthesia reduced heart rate range and average gain in both strains of rat.(ABSTRACT TRUNCATED AT 250 WORDS)

Dietary sodium loading elevates blood pressure in baroreceptor denervated rats

We have examined the possibility that defective baroreflex function may contribute to the hypertensive effect of a high dietary sodium intake. In a preliminary study we found that, after interrupting the baroreflex by sino-aortic denervation (SAD), feeding a high-sodium diet to normotensive Wistar/Kyoto rats (WKY) caused their tail-cuff blood pressure to rise to hypertensive levels. In the present study, SAD and sham-operated WKY were fed diets with either a low or a high sodium content. An increase in the sensitivity of blood pressure to sodium after baroreceptor denervation was confirmed by direct measurement of mean arterial pressure (MAP) in conscious rats via indwelling aortic catheters. After 8 weeks the MAP in SAD rats on the high sodium diet was 35 mm Hg higher than in SAD rats on the low sodium diet. Ganglion blockade reduced MAP to a similar level in all treatment groups, but pressor responses to phenylephrine were greater in SAD rats on the high sodium diet, suggesting that the hypertensive effect of sodium in this group might have been due to increased sympathetic vasoconstriction.

Restoration of depressed prostanoid-induced ileal contraction in spontaneously hypertensive rats by dietary fish oil

We have reported that dietary fish oil (FO) rich in n−3 PUFA modulates gut contractility. It was further demonstrated that the gut of spontaneously hypertensive rats (SHR) has a depressed contractility response to prostaglandins (PG) compared with normotensive Wistar-Kyoto (WKY) rats. We investigated whether feeding diets supplemented with n−3 PUFA increased gut contractility and restored the depressed prostanoid response in SHR gut. Thirteen-week-old SHR were fed diets containing fat at 5 g/100 g as coconut oil (CO), lard, canola oil containing 10% (w/w) n−3 FA as α-linolenic acid (18∶3n−3), or FO (as HiDHA®, 22∶6n−3) for 12 wk. A control WKY group was fed 5 g/100 g CO in the diet. As confirmed, the SHR CO group had a significantly lower gut response to PGE2 and PGF2α compared with the WKY CO group. Feeding FO increased the maximal contraction response to acetylcholine in the ileum compared with all diets and in the colon compared with lard, and restored the depressed response to PGE2 and PGF2α in the ileum but not the colon of SHR. FO feeding also led to a significant increase in gut total phospholipid n−3 PUFA as DHA (22∶6n−3) with lower n−6 PUFA as arachidonic acid (20∶4n−6). Canola feeding led to a small increase in ileal EPA (20∶5n−3) and DHA and in colonic DHA without affecting contractility. However, there was no change in ileal membrane muscarinic binding properties due to FO feeding. This report confirms that dietary FO increases muscarinic- and eicosanoid receptor-induced contractility in ileum and that the depressed prostanoid response in SHR ileum, but not colon, is restored by tissue incorporation of DHA as the active nutrient.

Chronic central administration of enalaprilat lowers blood pressure in stroke-prone spontaneously hypertensive rats

Earlier studies on the cardiovascular effects of intracerebroventricular (i.c.v.) administration of angiotensin converting enzyme (ACE) inhibitors implicate angiotensin II (AII) present in the central nervous system in the pathogenesis of hypertension. We have now examined whether central AII contributes to the maintenance of established hypertension in adult stroke-prone spontaneously hypertensive rats (SHRSP). The ACE inhibitor, enalaprilat, was infused i.c.v. for two weeks at a rate of 5 micrograms/h via osmotic minipumps. Control rats were either untreated or infused with saline. Mean arterial pressure (MAP), measured via an indwelling catheter, fell within 24 h in the enalaprilat-treated rats and remained at least 30 mmHg lower than in controls. This difference persisted after intravenous (i.v.) administration of a vasopressin (AVP) antagonist but was eliminated by subsequent ganglion blockade with i.v. pentolinium. Without prior administration of the AVP antagonist, however, the reductions of MAP after pentolinium were smaller. The reduction was still attenuated in treated rats compared with controls but there was a significant difference in the residual MAP. Circulating catecholamine levels were reduced by central ACE inhibition. However, pressor responsiveness to i.v. phenylephrine was unaffected. The results suggest that, in SHRSP, central ACE inhibition lowers blood pressure by reducing sympathetic outflow, implying that central AII has a tonic sympathoexcitatory effect in this strain.