D. Kentera

Effects of Verapamil and Aspirin on Experimental Chronic Hypoxic Pulmonary Hypertension and Right Ventricular Hypertrophy in Rats

Rats made hypoxic by confinement in hypoxic cages for 4 weeks developed pulmonary hypertension and right ventricular hypertrophy. Treatment with Verapamil or aspirin reduced both chronic hypoxic pulmonary hypertension and the hypertrophy of the right ventricle. The antihypertensive effect of Verapamil is explained by the involvement of the transmembrane calcium flux in pulmonary vascular smooth muscle in the hypoxic vasoconstrictory response. Part of the antihypertensive effect of inhibition of prostaglandin synthesis is attributed to a decrease in packed cell volume produced in hypoxic, aspirin treated rats.

The renin-angiotensin system in rats with hereditary hydronephrosis

SummaryThe renin-angotensin system was studied in rats suffering from hereditary hydronephrosis in which normal blood pressure, hyperkalemia, and damage to the renal medulla and distal tubules were found. An increased serum creatinine level, decreased creatinine clearance and increased 24 hrs urine volume were observed in rats with bilateral hydronephrosis. When compared to rats with normal kidneys, bilaterally hydronephrotic animals exhibited elevated plasma renin activity (9.9±1.3/S.E./ng AI/ml/hr vs. 2.4±0.4 in rats with normal kidneys), and decreased renal renin concentration (78±4 μg AII/g vs. 132±5). No correlation between the extent of kidney damage and renal renin concentration was found. After the hyperkalemia of the hydronephrotic rats was corrected, there were significant increases in both plasma renin activity and renal renin concentration, but the renal renin concentration remained significantly lower than that observed in animals with normal kidneys. The results suggest that renin production and/or storage capacity are diminished in hydronephrotic kidneys.

Decreased Pulmonary Pressor Response to Acute Hypoxia in Chronically Hypoxic Rats

The pulmonary vascular response to an acute hypoxic stimulus was examined in rats which were kept for 4 weeks in a hypoxic environment and compared to that of rats kept in a normoxic environment. To this end, the effects of breathing gas mixtures containing 7, 21 an 100% O2 on right ventricular systolic pressure (RVPs), cardiac output (Q) and calculated pulmonary vascular resistance (PVR) in chronically hypoxic (CH) rats and rats kept in a normoxic environment (N) were examined. During breathing of 21% O2 RVPs, Q, and PVR were all higher in CH than in N rats. Breathing a gas mixture containing 7% O2 had no effect on systemic blood pressure, heart rate or Q, in both CH and N rats. When compared to breathing of 21% O2, the RVP and PVR remained unchanged in CH rats breathing 7% O2, while both variables significantly (p less than 0.01) increased in N rats. The presented data indicate that the reaction of the pulmonary vasculature to an hypoxic challenge is decreased in CH rats.

Dynamics of regression of right ventricular hypertrophy in rats with hypoxic pulmonary hypertension.

Normobaric hypoxia caused a significant increase in right/left ventricular weight ratio in rats, a reliable indicator of hypertrophy of the right ventricle, already after 1 week of intermittent hypoxic confinement 7 days after termination of a 4-week hypoxic exposure the right/left ventricular weight ratio was significantly lower compared to the values immediately after hypoxic treatment. 8 weeks of sojourning in a normoxic environment were not sufficient to normalize the right ventricular systolic pressure and right/left ventricular weight ratio. It is concluded that changes in the right ventricular mass in rat is a fast reaction to the changes in pressure load.

Hypotensive effect of heparin on experimental chronic pulmonary hypertension in rats

SummaryDaily heparin injections (300 mg s.c.) during four weeks of hypoxic exposure resulted in a smaller rise in pulmonary artery pressure as compared with otherwise nontreated rats exposed to the same regimen of hypoxia.Heparin treatment did not significantly affect the systemic arterial pressure of the hypoxic rats.In spite of the different pressure load of the right ventricle after hypoxia in treated and control rats, there was no difference in parameters indicative of the degree of right ventricular hypertrophy between these two groups of hypoxic rats. This finding suggests that the difference in pressure load between the two groups of hypoxic rats occurred late in the course of hypoxic exposure.

Role of the renal medulla in the resistance of rats to salt hypertension

The role of the renal medulla in the sensitivity of rats to the hypertensive stimulus of salt overload was investigated in a strain of rats shown to be resistant to salt hypertension. Rats were divided into four groups: I-2/3 nephrectomy (medulla left intact); II — unilateral nephrectomy plus dissection of the medulla of the remaining kidney (UNDRM); III — UNDRM plus renomedullary autotransplantation; IV-— UNDRM plus renocortical autotransplantation. Two weeks after surgery all rats were given 1% NaCl solution instead of drinking water, and the blood pressure was measured every week for 6 weeks. The blood pressure, although increased, was significantly lower in groups I and III than in the other two groups throughout the period of salt loading. Renal excretory function was similarly altered in all rats, as indicated by similar plasma creatinine concentrations. The results indicate that antihypertensive activity of the renal medulla may account for the high resistance of the described rat substrain to salt hypertension.

Dependence of the hypertensive effect of chronic vanadate administration on renal excretory function in the rat.

The effect of vanadate, an agent that in rats exerts potent vasoconstrictor and diuretic action on blood pressure, cardiac output, total peripheral resistance and plasma and extracellular fluid volume, was investigated in normal rats and in rats with diminished renal excretory function. In normal rats, chronic dietary vanadate did not affect blood pressure, but induced an increase in total peripheral resistance and a decrease in cardiac output, plasma and extracellular fluid volume. In rats with diminished renal excretory function, vanadate increased blood pressure and total peripheral resistance without affecting cardiac output, plasma and extracellular fluid volume. The results indicate that this agent, with predominant vasoconstrictor action, does not cause sustained hypertension unless renal excretory function is diminished.

morphometric Studies on the Rat Renal Papilla of Resistant and Sensitive Strains in Partial Nephrectomy Salt Hypertension

The renomedullary interstitial cell (RIC) was studied morphometrically in the partial nephrectomy-salt (Chanutin-Ferris) model of hypertension. The RIC were compared in four strains of rat, two of them being resistant to the induction of this form of hypertension and two of them being sensitive. The Dahl salt-resistant (R/JR) rat was compared to a commercial Sprague-Dawley (SD) strain, and a Wistar derived strain discovered in Belgrade by Susic and Kentera (WB) was compared to a commercial Wistar strain (W). In both studies, resistance and sensitivity correlated well with the state of the RIC before the experimental procedure, the resistant strain having more numerous and better granulated RIC than the sensitive strain. It may therefore be possible to predict salt-resistance or sensitivity in rats by morphological examination of the RIC.

Suppressed antihypertensive function of the renal medulla in rats with spontaneous hypertension.

Several lines of evidence suggest that renomedullary tissue exerts a nonexcretory antihypertensive action (1,2, 3). Furthermore, it has been reported that manipulations of the kidney, such as ureteral ligation (4) or renal artery clipping (5) may induce a renomedullary deficiency which apparently contributes to the development of renoprival or Goldblatt hypertension, respectively. For example, in one kidney Goldblatt hypertension, clippingcinduced changes in renal hemodynamics and/or function appear to interfere with the antihypertensive function of the medulla which remains inside the clipped kidney, since in the same model, subperitoneal autotransplants of medullary tissue exert an antihypertensive action (5). From this evidence, it may be hypothesized that the renal dysfunction of spontaneously hypertensive rats (SH-rats) (6) could produce a renomedullary deficiency sufficient to induce the development of high blood pressure or to exacerbate pre-existing hypertension in this animal model. If this assumption is correct, extrarenal autotransplants of medullary tissue should protect SH-rats against hypertension.

Plasma renin activity and hypertrophy of the right ventricle in hypoxic rats.

SummaryA NaCl load in chronically hypoxic rats abolished the increase in plasma renin activity occurring in rats exposed to hypoxia of the same degree and duration but with normal NaCl intake.The parallel reduction in hypoxic hypertrophy of the right ventricle in NaCl-loaded rats could be considered as indirect evidence supporting the view that renin may be involved in the development of heart hypertrophy.ZusammenfassungKochsalzbelastung beseitigt bei chronisch-hypoxischen Ratten den Anstieg der Plasmarenin-Aktivität, welcher bei Ratten in Erscheinung tritt, die einer Hypoxie gleichen Grades und gleicher Dauer bei normaler Kochsalzaufnahme ausgesetzt sind.Die parallele Abnahme der hypoxisch bedingten Hypertrophie des rechten Ventrikels bei kochsalzbelasteten Ratten könnte als indirekter Beweis dafür betrachtet werden, daß Renin bei der Entwicklung der Herzhypertrophie eine Rolle spielt.