In hypothalamus as indicated in Fig column A

In hypothalamus, as indicated in Fig. 2 (column A) and following the enzymatic cascade represented in Fig. 1, we could hypothesize a predominance of Ang 2–10 and Ang III formation in SHR compared to WKY. This is in agreement with previous results that reported significant higher rate of Ang 2–10 formation in hypertensive than in the normotensive rats [45]. The reduction in vasopressinase activity together with the assumption that hypothalamic Ang III is responsible for the neurosecretion of Cyclophosphamide from neurohypophysis [20] strongly support a predominance of ADH in hypothalamus of SHR in comparison with hypothalamus of WKY. In plasma, the inverse response of aminopeptidases may suggest a predominance of Ang II and Ang IV in SHR compared to WKY (Fig. 2 column E). Previous data on the RAS components in normotensive and hypertensive rats were variable and did not help to clarify convincingly the differences between both groups. In studies performed in animals of similar age than in the present ones, no differences were reported between WKY and SHR in hypothalamus and plasma neither in angiotensin-converting enzyme (ACE) [9] nor in angiotensinogen [14]. Plasma Ang II levels were higher in SHR than in WKY and the expression levels of ACE mRNA in hypothalamus were also higher in SHR but no differences were observed between SHR and WKY in the expression levels of AT1 mRNA [54]. Comparing SHR with normotensive Donryu rats, while renin, Ang II and ACE decreased in plasma of SHR, angiotensinogen increased but Ang I did not change. In hypothalamus, there were no differences between normotensive and hypertensive rats for Ang II levels [5]. Regarding ADH, a divergence has been also observed between hypothalamus and plasma: while WKY demonstrated lower ADH levels than SHR in plasma, WKY had higher levels in the paraventricular nucleus than SHR [27]. SHR-PR compared with WKY-PR (Fig. 2 column B) suggested a preponderance of Ang III formation and a reduction of Ang IV that, together with a decreased vasopressinase activity, leads to a possible increased ADH in hypothalamus. In plasma, this comparison (Fig. 2 column F) suggests a predominance of Ang 2–10 and Ang IV. Results from the literature do not clarify the influence of propranolol on RAS: while a reduced renin secretion after propranolol treatment was described by Zhang et al. [58], causing reduced levels of Ang I and Ang II formation [52], others authors reported a reduction of plasma renin activity but no change of ACE in normotensive rats [16]. The subsequent metabolism of Ang I and Ang II, depending on the aminopeptidase activities, is the first objective of the present work. SHR had higher systolic blood pressure values than both WKY in control and propranolol-treated rats (Fig. 3). However, propranolol, at the dose used here did not influence systolic blood pressure neither in WKY or in SHR. Regardless of the influence of propranolol on systolic blood pressure, for which different results have been reported [8], [10], [36], [43], [48] and therefore still remains a debatable theme, its inhibitory effect on sympathetic nerve activity is well recognized [48]. The analysis of its effect on hypothalamus and plasma is our objective in the present study. In addition to the possible influence on the obtained results of drug dosage, differences in gender, diet, supplier or strains provided, the age of the animals could also be determinant. Some authors who did not obtain a reduction in blood pressure, like in the present study, used animals around 10–12weeks of age [8], in contrast to those who obtained a reduction in systolic blood pressure who were using animals 16weeks old or more [47], [50]. At 12weeks of age, both WKY and SHR are close to reach the plateau of maximum systolic blood pressure levels, but they are still increasing [19], [21], [28]. This condition may also account for the discrepancy in the results obtained for systolic blood pressure after propranolol treatment among different authors.