Blood pressure responses of conscious normotensive and spontaneously hypertensive rats to intracerebroventricular and peripheral administration of captopril.

Abstract

SUMMARYIn conscious spontaneously hypertensive rats, intracerebroTentricular injection of captopril (2 rag/kg) resulted in a rapid hypotenshe response that lasted several hours. The same dose given by Intracerebroventricular injection had no significant effect on blood pressure (BP) of normotensive Wistar-Kyoto (WK) rats over 7 hours. There was no significant change in BP of conscious spontaneously hypertensive rats (SHR) in response to Intracerebroventricular injection of vehicle and only a transitory fall in BP in response to intravenous injection of captopril (2 mg/kg). There was no significant differences between plasma renin activity (PRA) of conscious norrootenslve WKY rats and the PRA of SHR. These results suggest biochemical differences between the brains of SHR and normotensive WKY control rats. These differences could involve the brain renin-angiotensin system or other iteuropeptides. renin-angiotensin system in the brain has been the subject of some controversy.

Local generation and release of angiotensin II in peripheral vascular tissue.

“…Captopril caused a significant increase in irAng I release, from a control value of 626.6 ± 22.1 to 867. 8 injection, release of the two peptides tended to return toward their basal levels.…”

“…16 ' " After extraction of the perfusate by the Sep-Pak C 18 cartridges, the eluted and dried materials were dissolved in 250 (JL\ of 0.1% TFA and chromatographed on a Vydac C, 8 reverse-phase column (0.46 x 25 cm, The Separation Group, Hesperia, CA, USA). The elution was performed with an exponential gradient of methanol from 28 to 80% in 10 mM sodium acetate buffer, pH 5.6, over a period of 23 minutes at a flow rate of 1 ml/min, and 200-ptl fractions were collected and dried in a vacuum centrifuge.…”

“…Recently, intravenous administration of renin inhibitor was found to reduce blood pressure in a dose-dependent fashion in dogs with completely suppressed plasma renin. 10 More recently, Okamura et al" demonstrated that the ACE inhibitorenalapril and Ang II antagonist [Sar',Ile 8 ]Ang II lowered the blood pressure of rats in the chronic stage of two-kidney, one clip hypertension when plasma renin activity was almost normal. These findings raise an intriguing hypothesis that the vascular reninangiotensin system plays an important role in the maintenance of hypertension, though direct evidence is lacking.…”

Pharmacodynamics of converting enzyme inhibition: the cardiovascular, endocrine and autonomic effects of MK421 (enalapril) and MK521.

“…Many tissue effects on kidney (Hollenberg et al, 1979;Wong & Zimmerman, 1981), brain (Suzuki et al, 1981;Hutchinson et al, 1980), adrenal and vessels Collis & Keddie, 1981) have been described and some of these are not obviously directly related to converting enzyme inhibition or its secondary effects. There is also continuing debate on the relative contributions to the haemodynamic responses made by depressed levels of angiotensin II or increased levels of kinins, resulting from enzyme inhibition .…”

Effect of lesions of the anteroventral third ventricle (AV3V) on the development of hypertension in spontaneously hypertensive rats.

“…8 Moreover, surgical transection of the brain or spinal cord lowers blood pressure to a greater extent in the SHR than in normotensive Wistar-Kyoto (WKY) control animals. 4 -6 Recent evidence has pointed toward a role for the brain renin-angiotensin system in the hypertension of SHR" since these rats show greater pressor responses to centrally administered All when compared to WKY controls; 7 also, central pharmacologic blockade of All receptors 8 -9 or Allconverting enzyme 10 lowers arterial pressure in SHR but not WKY.…”