Influence of Age on Cardiovascular Effects of Increased Dietary Sodium and Angiotensin-converting Enzyme Inhibiton in Normotensive Wistar Rats

Recent studies have shown that increased intake of dietary sodium chloride produces blood pressure-independent increase in cardiac and renal mass even in young normotensive rats. With advancing age the harmful cardiovascular effects of increased dietary sodium are not so well known. In the present study the influence of advancing age on the cardiovascular effects of increased intake of sodium (control diet, 0.3% and high-sodium diet, 2.6% sodium in the chow) were examined in young and aged (3 and 18 months old, respectively, at the beginning of the experiment) male normotensive Wistar rats in a six-week study. Moreover, the potential role of renin-angiotensin system in ageing during normal and a high-sodium intake was studied using a pharmacological tool, angiotensin converting enzyme (ACE) inhibitor ramipril. Ageing did not significantly modify basal systolic blood pressure measured by the tail cuff method. A high intake of sodium chloride increased blood pressure significantly only in aged rats, while in young rats it increased renal weight. Left ventricular weight was not affected by high-sodium diet in either age group. The ACE inhibition during control diet lowered blood pressure and decreased left ventricular weight in young rats only and these effects were completely blocked by a high-sodium diet. The maximal vascular contraction force of mesenteric arterial rings to noradrenaline was decreased with ageing while endothelium-dependent and -independent relaxation responses were unaltered with ageing. The sensitivity to sodium nitroprusside was impaired by the high-sodium diet in young rats. In both age groups the urinary excretion of calcium was increased during the high-sodium diet. In conclusion, the increased intake of sodium produced different changes in cardiovascular function in normotensive rats depending on age. With advancing age, the sensitivity to sodium-induced increase in blood pressure was increased. In aged rats a high intake of dietary sodium elevated blood pressure, while in young rats it increased renal mass without increase in blood pressure. In both age groups sodium did not affect left ventricular hypertrophy. Both high-sodium intake and ageing attenuated or even abolished the cardiovascular effects of ACE inhibition.     

The effect of centrally administered TRH on blood pressure,heart rate and ventilation in rat

Different doses (3, 16, 80, 400 and 2000 ng per rat) of TRH or alternatively saline were infused into the lateral ventricle of urethane-ahaesthetized rats and blood pressure, heart rate, respiration rate and tidal volume were recorded. A dose of 3 ng TRH caused a significant elevation of blood pressure and heart rate, whereas 16 ng was needed for respiration rate to be elevated. There was no change in respiratory minute volume during the experiment. We conclude that TRH has profound physiological effects and that TRH, given centrally, is a potent hypertensive, chronotropic and tachypnoeic agent.     

Acute Cardiovascular Effects of Intravenous Cimetidine

ABSTRACT To assess the acute cardiovascular effects of cimetidine—a widely used histamine-H₍₂₎-receptor antagonist—cuff arterial blood pressure, M-mode echocardiogram of the left ventricle and systolic time intervals were recorded in 10 healthy volunteers before and after 200 mg of cimetidine or isotonic saline given intravenously in a double-blind crossover manner. Neither echocardiograms nor systolic time intervals revealed any significant effects of cimetidine on the left ventricular performance. However, cimetidine decreased slightly the systolic arterial pressure. The maximal effect of cimetidine (7±1 mmHg, mean ± SEM) differed significantly from that of saline (3±1 mmHg, p<0.02). When compared with the pre-injection level, the calculated total peripheral resistance decreased significantly after cimetidine (p<0.01), whereas saline induced no such change. We conclude that a bolus injection of cimetidine does not impair cardiac performance but may induce transient hypotension due to reduction of the total peripheral resistance. This reduction can explain the hypotensive effect of i.v. cimetidine reported in acutely ill patients.     

Effects of Potassium-channel Opener HOE 234 in Guinea-pig Airways

The mechanism of the bronchospasmolytic effect of HOE 234 ((3S,4R)-3-hydroxy-2,2-dimethyl-4-(2-oxo-1-pyrrolidinyl)-6-phenylsulphonylchromane hemihydrate), a novel opener of ATP-sensitive potassium channels, has been studied by in-vitro testing in ring preparations of trachea and different parts of the principle bronchus of guinea-pigs, using methacholine, histamine and KCl as preconstrictors. The contribution of prostanoids was estimated in the presence and absence of indomethacin. Regional differences in the bronchodilatory effect of HOE 234 were compared with that of salbutamol. HOE 234 had a concentration-dependent relaxing effect on the smooth muscle preparations. In the absence of indomethacin no regional differences were seen for the effect of HOE 234 against the metacholine or KCl preconstriction, whereas with histamine a particularly strong relaxation was detectable in trachea. In the presence of indomethacin, distal bronchus after methacholine and trachea after KCl preconstriction were relaxed significantly more strongly than the other parts. The relaxation of the histamine-constricted trachea rings was not increased in comparison with that without indomethacin pretreatment. Thus the bronchospasmolytic effect of HOE 234 varied depending on the pretreatment, method of preconstriction and part of the airways examined. It was strongest in trachea rings with histamine preconstriction but its potency was clearly less than that of salbutamol. The latter had regionally different effects, being stronger in trachea than in the bronchi for all methods of preconstriction. The results suggest that the formation of bronchoconstricting prostanoids can attenuate parts of the relaxing effect of HOE 234. The possible advantages of HOE 234 as an anti-asthma drug might be related to an effect on bronchial hyper-reactivity and mucus secretion, because as a direct bronchodilator it is inferior to salbutamol.