Effect of captopril and hydralazine on arterial pressure-urinary output relationships in spontaneously hypertensive rats.

Abstract

SUMMARY Angiotensin I converting enzyme inhibitors are typically classified as peripheral vasodilators. We studied the effect of captopril and a known vasodilator, hydralazine, on arterial pressure-urinary output relationships in adult spontaneously hypertensive rats to determine whether these drugs produced similar changes in this relationship. Tail-cuff pressure and 24-hour urine output and sodium excretion were measured under steady state conditions during ingestion of tap water or saline (1% NaCI) ad libitum. Sodium intake increased seven to nine times when rats drank saline, but in the absence of drug treatment, tail-cuff pressure was not altered significantly (water, 213 ± 3 vs saline, 220 ± 5 mm Hg). Daily administration of captopril (100 mg/kg p.o.) or hydralazine (15 mg/kg p.o.) for 2 weeks lowered tail-cuff pressure significantly (175 ± 3 and 166 ± 3 mm Hg, respectively; p<0.01) while rats drank tap water. Continued administration of hydralazine plus 2 weeks of drinking saline did not alter tail-cuff pressure (162 ± 4 mm Hg), but with the addition of saline during captopril treatment, tail-cuff pressure was elevated significantly (210 ± 5 mm Hg; p<0.01). Thus, hydralazine produced a parallel shift of the arterial pressure-urinary output relationship along the pressure axis. In contrast, captopril produced a marked change in the slope of this relationship, making arterial pressure extremely salt-sensitive. The results suggest that the two drugs have different effects on the mechanisms that contribute to the long-term control of arterial pressure. The changes associated with captopril treatment are consistent with the removal of the normal renal effects of the renin-angiotensin system, rather than with a nonspecific peripheral vasodilation. (Hypertension 10: 590-594, 1987) KEY WORDS • renal function curve • sodium excretion • sodium sensitivity antihypertensive drugs • captopril • spontaneously hypertensive rats A LTHOUGH numerous types of drugs are effec-/ \ tive in treating primary hypertension, the A. \ -physiological changes leading to the decrease in arterial pressure during administration of these drugs are not well documented. One of the major obstacles to understanding the mechanism of action of antihypertensive agents is the failure to adequately describe the pathophysiology of hypertension. Using a systems analysis approach, Guyton et al.1 have provided a useful conceptual framework for understanding the long-term control of the circulation in normal and abnormal conditions, including hypertension. According to the predictions of their model, the ability of Received March 27, 1987; accepted July 15, 1987. the kidneys to excrete sodium and water is a primary determinant of the long-term steady state level of arterial pressure. 2 -3 The importance of pressure-diuresis and pressure-natriuresis to the long-term control of arterial pressure has recently been reviewed. 4 This relationship between arterial pressure and excretion of sodium and water by the kidneys, called the renal function curve...

Effects of salt loading and various therapies on cardiac hypertrophy and fibrosis in young spontaneously hypertensive rats

“…A significant antihypertensive effect of captopril at the same dose as we used was reported in SHR by Guidi and Hollenberg (1987). However, salt loading was repeatedly demonstrated to attenuate the effects of captopril (Kline and Mercer, 1987;Wyss et al, 1994). Salt depletion enhanced the antihypertensive effect of captopril (Migdalof et al, 1984).…”

Glomerular function reserve and sodium sensitivity

“…146 Experimental models for diabetes mellitus have not been tested for sodium sensitivity, but human studies suggest high sodium sensitivity in this condition. [147][148][149][150][151] On the other hand, it is known that Goldblatt models 152,153 and spontaneously hypertensive rats (SHR) of Kyoto strain 152,154 are not sodium-sensitive. Table 2 clearly shows that, in all animal models categorized as "sodiumsensitive", the glomerular capillary pressure is elevated, strongly supporting a linkage between sodium sensitivity and glomerular hypertension.…”

Σχεση Νατριου Ουρων Εικοσιτετραωρου Και Μεσης Αρτηριακης Πιεσης Μετα Τη Χορηγηση Αντιυπερτασικων Φαρμακων

“…Στην περίπτωση αυτή πιστεύεται οτι παρόλο που το ορμονικό σκέλος του συστήματος είναι σε καταστολή συνεπεία διαστολής του εξωκυτταρίου χώρου, το ιστικο σκέλος υπερλειτουργεϊ. Εναντίον όμως της άποψης αυτής είναι το γεγονός οτι η επίδραση της καπτοπρίλης στην θέση και κλίση της καμπύλης νεφρικής λειτουργίας είναι διαφορετική από εκείνη των καθαρώς περιφερικών αγγειοδιασταλτικών φαρμάκων όπως η υδραλαζίνη 145 συνεπώς η δράση της καπτοπρίλης δεν είναι δυνατόν να αποδοθεί αποκλειστικά τουλάχιστον, στην επίδραση της κατ'ευθείαν στις λείες μυϊκές ίνες των αγγείων αντίστασης.…”