Effects of verapamil and converting enzyme inhibition on bilateral renal function of two-kidney, one-clip hypertensive rats

1987 ◽  
Vol 72 (6) ◽  
pp. 657-667 ◽  
Author(s):  
David W. Ploth ◽  
Kurt Kleeman ◽  
Linell Morrill ◽  
Ricardo Rademacher ◽  
Cynthia A. Jackson
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Enzyme Inhibitor ◽  
Blood Pressure Reduction ◽  
Control Period ◽  
Converting Enzyme ◽  
Hypertensive Rats ◽  
Filtration Fraction ◽  
P Values ◽  
Renal Vascular

1. Experiments were conducted in two-kidney, one-clip renal vascular hypertensive rats (GHR) to assess the responses of each kidney to acute treatment with the antihypertensive calcium channel blocking agent verapamil in the presence and in the absence of converting enzyme inhibitor (CEI). One group of GHR (0.2 mm inner diam. clip 3 weeks before study) were examined during a control period, and during a second period of infusion of verapamil (600 μg h−1 kg−1). A second group of GHR were examined during a control period, during CEI (teprotide, 3 mg h−1 kg−1) infusion and during a third period of verapamil (600 μg h−1 kg−1) infusion superimposed on CEI infusion. 2. Although systemic blood pressure (BP) decreased from 175 ± 4 to 149 ± 5 mmHg (mean ± SEM) in response to verapamil alone, renal blood flow for non-clipped kidneys increased from 5.9 ± 0.4 to 6.5 ± 0.3 ml/min, indicating a 30% reduction of renal vascular resistance (P values 0.01; n = 9). Glomerular filtration rate (GFR) for non-clipped kidneys (n = 24) increased from 0.91 ± 0.09 to 1.47 ± 0.14 ml/min and filtration fraction increased from 0.32 ± 0.04 to 0.47 ± 0.03 (P values 0.05). Urine flow rate and absolute and fractional sodium excretion for non-clipped kidneys increased. GFR for clipped kidneys decreased during verapamil. 3. Treatment with CEI alone resulted in nearly identical responses of BP and function of the non-clipped kidney, except filtration fraction was unchanged. The addition of verapamil to ongoing converting enzyme blockade tended to augment the increased GFR of the non-clipped kidney. 4. Plasma renin activity (PRA) increased from 30 ± 3 to 59 ± 7 ng of angiotensin (ANG) I h−1 ml−1 with verapamil alone, a significantly larger increment than the increase of PRA from 27 ± 5 to 39 ± 9 ng of ANG I h−1 ml−1 in GHR subjected to comparable blood pressure reduction by mechanical aortic constriction. 5. Verapamil resulted in many similar effects on renal function to those observed during blockade of converting enzyme. The increased filtration fraction observed in response to verapamil may be the result of vasodilatation of the afferent arteriole or of an increase in the glomerular ultrafiltration coefficient.

High-potassium diet attenuates salt-induced acceleration of hypertension in SHR

1991 ◽  
Vol 260 (1) ◽  
pp. R21-R26 ◽  
Author(s):  
Y. Sato ◽  
K. Ando ◽  
E. Ogata ◽  
T. Fujita
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
High Potassium ◽  
Spontaneously Hypertensive ◽  
Antihypertensive Action ◽  
High K ◽  
Wistar Kyoto ◽  
Renal Vascular

We studied the effects of K supplementation (8% KCl) for 4 wk on blood pressure (BP), Na space, and renal hemodynamics in 5-wk-old, spontaneously hypertensive rats (SHR) or age-matched Wistar-Kyoto rats (WKY) eating normal-NaCl (0.66%) or high-NaCl (8%) diet. In WKY, high-Na and/or high-K diets had no effects on BP. In SHR, Na load accelerated the development of hypertension, whereas K supplementation did not affect BP of normal-Na SHR but attenuated the increase in BP with Na load. Correspondingly, Na load in SHR significantly increased renal vascular resistance (RVR), and K supplementation attenuated the increased RVR of Na-loaded SHR. Moreover, Na space of SHR was increased compared with that of WKY, and although Na load did not affect Na space, K supplementation tended to decrease Na space in SHR. These results indicate that 9-wk-old SHR is relatively volume-expanded compared with age-matched WKY, and K supplementation could improve the lowered slope of the pressure-Na excretion relationship in SHR, resulting in maintenance of Na balance. Thus the data suggest that changes in RVR, which might be intimately related to renal function for Na excretion, contribute to both salt sensitivity of SHR and antihypertensive action of K supplementation in Na-loaded SHR.

Renal vasodilatation after inhibition of renin or converting enzyme in marmoset

1986 ◽  
Vol 251 (5) ◽  
pp. H897-H902
Author(s):  
D. Neisius ◽  
J. M. Wood ◽  
K. G. Hofbauer
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Angiotensin Ii ◽  
Renal Blood Flow ◽  
Vascular Resistance ◽  
Enzyme Inhibitor ◽  
Renal Vascular Resistance ◽  
Converting Enzyme ◽  
Renin Inhibition ◽  
Renal Vascular

The relative importance of angiotensin II for the renal vasodilatory response after converting-enzyme inhibition was evaluated by a comparison of the effects of converting-enzyme and renin inhibition on renal vascular resistance. Renal, mesenteric, and hindquarter blood flows were measured with chronically implanted ultrasonic-pulsed Doppler flow probes in conscious, mildly volume-depleted marmosets after administration of a converting-enzyme inhibitor (enalaprilat, 2 mg/kg iv), a synthetic renin inhibitor (CGP 29,287, 1 mg/kg iv), or a renin-inhibitory monoclonal antibody (R-3-36-16, 0.1 mg/kg iv). Enalaprilat reduced blood pressure (-16 +/- 4 mmHg, n = 6) and induced a selective increase in renal blood flow (27 +/- 8%, n = 6). CGP 29,287 and R-3-36-16 induced comparable reductions in blood pressure (-16 +/- 4 mmHg, n = 6 and -20 +/- 4 mmHg, n = 5, respectively) and selective increases in renal blood flow (36 +/- 12%, n = 6 and 34 +/- 16%, n = 4, respectively). The decrease in renal vascular resistance was of similar magnitude for all of the inhibitors (enalaprilat -28 +/- 3%, CGP 29,287 -32 +/- 6%; and R-3-36-16 -33 +/- 7%). These results indicate that the renal vasodilatation induced after converting-enzyme or renin inhibition is mainly due to decreased formation of angiotensin II.

Antihypertensive and renal effects of cilazapril and their reversal by angiotensin in renovascular hypertensive rats

1988 ◽  
Vol 74 (4) ◽  
pp. 365-372 ◽  
Author(s):  
Yu-An Ding ◽  
Shin-Tsu Chang ◽  
Shyh-Ming Shieh ◽  
Wann-Chu Huang
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Angiotensin Ii ◽  
Enzyme Inhibitor ◽  
Fractional Excretion ◽  
Hypotensive Effect ◽  
Hypertensive Rats ◽  
Renal Effects ◽  
Angiotensin Iii ◽  
Excretion Rates

1. The antihypertensive and renal effects of cilazapril, a new angiotensin converting enzyme inhibitor, were evaluated in both two-kidney, one-clip Goldblatt hypertensive rats (n = 11) and normotensive rats (n = 6). 2. Intravenous infusion of cilazapril (1 mg/kg followed by 25 μg min−1 kg−1) caused significant reductions of blood pressure from 163 ± 3 to 122 ± 4 mmHg and from 157 ± 2 to 113 ± 3 mmHg in two separate groups of hypertensive rats and from 124 ± 1 to 105 ± 2 mmHg in normotensive rats. The hypotensive effect in terms of absolute value or percentage change was greater in hypertensive rats than in normotensive rats (41 ± 6 vs 20 ± 3 mmHg or 25 ± 4% vs 16 ± 2%, respectively). 3. Cilazapril increased glomerular filtration rate, urine flow, and absolute and fractional excretion rates of sodium and potassium in the non-clipped kidney of hypertensive rats. In contrast, the clipped kidney exhibited a depressed renal function during cilazapril infusion. 4. In normotensive rats, the hypotensive and enhanced renal function responses to cilazapril were much less than those of the non-clipped kidney of hypertensive rats. 5. Superimposed administration of either angiotensin II or angiotensin III during cilazapril infusion completely reversed the blood pressure and bilateral renal responses of cilazapril in both hypertensive and normotensive rats. 6. These results indicate that cilazapril reduces arterial pressure and enhances renal excretion mainly via inhibition of angiotensin II and angiotensin III formation.

The Relationship Between Angiotensin II (ANG II) and Oxidative Stress in the Maintenance of Mean Arterial Pressure (MAP) of Spontaneously Hypertensive Rats.

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 686-686
Author(s):  
Rodney J Bolterman ◽  
Clara M Ortiz-Ruiz ◽  
Luis A Juncos ◽  
Jane F Reckelhoff ◽  
Juan C Romero
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Plasma Levels ◽  
Spontaneously Hypertensive Rats ◽  
Enzyme Inhibitor ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Converting Enzyme Inhibitor

48 Spontaneously hypertensive rats (SHR) reportedly have inappropriately high levels of Ang II despite normal plasma renin activity (PRA). Because Ang II stimulates oxidative stress, which in turn quenches nitric oxide, it is possible that Ang II-induced increases in oxidative stress contribute to the increase in blood pressure. Indeed, administering either a converting enzyme inhibitor (to decrease Ang II) or Tempol (a potent antioxidant) reduces blood pressure in SHR. We tested whether decreasing Ang II with a converting enzyme inhibitor reduces oxidative stress as well as MAP in SHR. For this, we divided 12 weeks old SHR into two groups (n=5 each). One group was treated with captopril (100 mg/kg/day added to the drinking water) and the other served as our untreated time controls. After 16 days of treatment, the rats were anesthetised and we measured MAP and collected blood samples to determine PRA, and the plasma levels of Ang II and thiobarbituric acid-reactive substances (TBARS). The captopril-treated rats had a lower MAP than the untreated rats (92±4 vs. 160±5 mmHg, respectively) and an increased PRA (42±1 vs. 26±6 ng/ml/h; captopril-treated vs. untreated rats, respectively). The decreased MAP in the captopril-treated SHR was accompanied by reduced plasma levels of Ang II (630±47 vs. 836±205 pg/ml) and TBARS (5.4±1.0 vs. 3.0±0.2 nmol/ml). Despite the significant decrease in Ang II levels in the captopril-treated SHR, they are still 20-fold higher rhan in normotensive Sprague-Dawley rats (34.0±8.8 pg/ml). In summary, captopril-induced decreases of MAP in SHR are accompanied not only by reduced levels of Ang II, but also by reduced oxidative stress. Because antioxidants also lower MAP in SHR, it suggests that oxidative stress induced by Ang II may play a role in the pathogenesis of the increased blood pressure in SHR.

Effects of benazepril, an angiotensin-converting enzyme inhibitor, combined with CGS 35066, a selective endothelin-converting enzyme inhibitor, on arterial blood pressure in normotensive and spontaneously hypertensive rats

2002 ◽  
Vol 103 (s2002) ◽  
pp. 363S-366S ◽  
Author(s):  
Bruno BATTISTINI ◽  
Bilal AYACH ◽  
Stéphanie MOLEZ ◽  
Andre BLOUIN ◽  
Arco Y. JENG
Keyword(s):  
Blood Pressure ◽  
Angiotensin Converting Enzyme ◽  
Spontaneously Hypertensive Rats ◽  
Ace Inhibitor ◽  
Enzyme Inhibitor ◽  
Converting Enzyme ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Arterial Blood ◽  
Endothelin Converting Enzyme

Continuous intra-arterial administration of a selective endothelin-converting enzyme (ECE) inhibitor CGS 35066 at a dose of 30mg/kg decreased the mean arterial blood pressure (MABP) in conscious unrestrained normotensive rats and spontaneously hypertensive rats (SHRs). At that dose, the magnitude of the antihypertensive effects was greater in SHRs than in normotensive rats. Additional administration of an angiotensin-converting enzyme (ACE) inhibitor benazapril (lotensin) further reduced MABP in normotensive rats and completely blocked hypertension in SHRs. However, when the selective ECE inhibitor was subsequently removed, blood pressure was less inhibited in normotenive rats whereas it remained strongly inhibited in SHRs by the ACE inhibitor alone. These results imply that simultaneous treatment with benazepril and CGS 35066 gave additive antihypertensive effects in normotensive rats but not in SHRs, when both compounds were administered at a dose of 30mg/kg. Our results suggest that: (i) the endothelin (ET) system together with the renin–angiotensin system contribute to the maintenance of blood pressure in normal healthy rats; (ii) while an ECE inhibitor acts as an antihypertensive agent on its own, the sole efficacy of ACE inhibitor at that dose is sufficient to block MABP without the participation of the ET system in SHR.

Sign in / Sign up

Export Citation Format

Share Document