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.

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.

THE EFFECT OF FOETAL REMOVAL ON THE BLOOD PRESSURE IN STEROID HYPERTENSIVE RATS

1971 ◽  
Vol 67 (3) ◽  
pp. 590-596 ◽  
Author(s):  
H. C. Moore ◽  
J. Borvendeg ◽  
K. Wilson
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Hypotensive Effect ◽  
The Other ◽  
Hypertensive Rats ◽  
Pregnancy Hypertension ◽  
Human Pregnancy ◽  
Other Hand ◽  
Metrial Gland

ABSTRACT In unilaterally nephrectomized hypertensive rats receiving DOCA, cortisone and saline the blood pressure falls after the removal of the foetuses as though the animals continued to be pregnant with the foetuses in situ. On the other hand, when the foetuses are removed from steroid hypertensive animals in which the maternal kidneys remain intact the blood pressure remains at hypertensive levels. The metrial gland part of the placenta appears histologically viable after foetal removal. We conclude from the present and earlier experiments that the usual hypotensive effect of pregnancy in hypertensive animals is due to a vasodepressor agent produced by the foetuses and the metrial gland moiety of the placenta and that the activity of this agent is subject to maternal renal function. A relation between these experiments and human pregnancy hypertension is not clear but we suggest that in human pregnancy, hypertension could be due either to failure of the foetoplacental vasodepressor or vasodilator agent or to destruction or excretion of this agent by the maternal kidney.

Renal function contributes to antihypertensive effect of vasopressin in DOCA-salt but not spontaneous hypertension

1994 ◽  
Vol 267 (5) ◽  
pp. H1842-H1850
Author(s):  
H. Wang ◽  
J. R. McNeill
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Spontaneously Hypertensive Rats ◽  
Antihypertensive Effect ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Vasopressin Infusion ◽  
Hypertensive Group ◽  
Excretion Rates ◽  
Dramatic Fall

The contribution of sodium losses to the dramatic fall in blood pressure that follows cessation of a 3-h intravenous infusion of vasopressin (20 ng.kg-1.min-1) in hypertensive rats was investigated. Cessation of the vasopressin infusion was associated with a large fall in pressure below preinfusion basal levels (30-50 mmHg) in both spontaneously hypertensive rats (SHR) and deoxycorticosterone acetate (DOCA)-salt-hypertensive rats. In contrast, pressure returned to control levels in normotensive rats. Sodium excretion rates increased markedly during the infusions of vasopressin in both SHR and DOCA-salt-hypertensive rats but also in their appropriate normotensive controls. An equinatriuretic dose of furosemide failed to induce any change in pressure in SHR or normotensive controls. In contrast, furosemide decreased pressure in the DOCA-salt-hypertensive group, although the decrease was not as large as with vasopressin. Replacement of the sodium losses that occurred during the vasopressin infusion failed to return pressure toward control levels in SHR but did increase pressure in the DOCA-salt-hypertensive group. The results indicate a major difference between the SHR and DOCA-salt-hypertensive models. In SHR, sodium losses do not contribute to the antihypertensive effect of vasopressin, but in contrast these losses do contribute significantly to this antihypertensive effect in the DOCA-salt-hypertensive model.

THE FALL OF BLOOD PRESSURE FOLLOWING INDUCTION OF DECIDUOMATA IN STEROID HYPERTENSIVE RATS RECEIVING PROGESTERONE

1968 ◽  
Vol 59 (2) ◽  
pp. 227-234 ◽  
Author(s):  
H. C. Moore ◽  
I. Cserhati ◽  
F. P. Biliczki
Keyword(s):  
Blood Pressure ◽  
Hypotensive Effect ◽  
Hypertensive Rats ◽  
Pregnant Rats ◽  
Hypertensive Rat ◽  
Equivalent Time ◽  
Metrial Gland ◽  
Blood Pressure Responses ◽  
A Minor ◽  
Maternal Decidua

ABSTRACT Experimental deciduomata and progesterone together lower the blood pressure in the steroid hypertensive rat from the 5th to 10th day of decidual growth i. e. from the 10th to 15th day of pseudopregnancy. This would suggest that the fall of blood pressure at an equivalent time of gestation in hypertensive pregnant rats could be due to the maternal decidua under the influence of progesterone. It is further considered that the metrial gland of the deciduoma is more likely to be responsible for the hypotensive effect and by comparison that the metrial gland is implicated in the hypotensive effect of pregnancy. Progesterone alone also exerts a minor hypotensive effect in those animals in which a nephrectomy forms part of the hypertension regimen and indicates one way in which a maternal renal factor could influence blood pressure responses in hypertensive pregnant rats.

scholarly journals Deletion of proton-sensing receptor GPR4 associates with lower blood pressure and lower binding of angiotensin II receptor in SFO

2016 ◽  
Vol 311 (6) ◽  
pp. F1260-F1266 ◽  
Author(s):  
Xuming Sun ◽  
Ellen Tommasi ◽  
Doris Molina ◽  
Renu Sah ◽  
K. Bridget Brosnihan ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Fractional Excretion ◽  
Urine Osmolality ◽  
Brain Regions ◽  
Lower Blood Pressure ◽  
Angiotensin Ii Receptor ◽  
Lower Blood ◽  
Fractional Excretion Of Sodium ◽  
The Impact

Diets rich in grains and meat and low in fruits and vegetables (acid-producing diets) associate with incident hypertension, whereas vegetarian diets associate with lower blood pressure (BP). However, the pathways that sense and mediate the effects of acid-producing diets on BP are unknown. Here, we examined the impact of the deletion of an acid sensor GPR4 on BP. GPR4 is a proton-sensing G protein-coupled receptor and an acid sensor in brain, kidney, and blood vessels. We found that GPR4 mRNA was higher in subfornical organ (SFO) than other brain regions. GPR4 protein was abundant in SFO and present in capillaries throughout the brain. Since SFO partakes in BP regulation through the renin-angiotensin system (RAS), we measured BP in GPR4−/− and GPR4+/+ mice and found that GPR4 deletion associated with lower systolic BP: 87 ± 1 mmHg in GPR4−/− ( n = 35) vs. 99 ± 2 mmHg ( n = 29) in GPR4+/+; P < 0.0001, irrespective of age and sex. Angiotensin II receptors detected by 125I-Sarthran binding were lower in GPR4−/− than GPR4+/+ mice in SFO and in paraventricular nucleus of hypothalamus. Circulating angiotensin peptides were comparable in GPR4−/− and GPR4+/+ mice, as were water intake and excretion, serum and urine osmolality, and fractional excretion of sodium, potassium, or chloride. A mild metabolic acidosis present in GPR4−/− mice did not associate with elevated BP, implying that deficiency of GPR4 may preclude the effect of chronic acidosis on BP. Collectively, these results posit the acid sensor GPR4 as a novel component of central BP control through interactions with the RAS.

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