Renal Hemodynamic Effects of Tertatolol Compared with Those of Propranolol in the Conscious Dog

Abstract

Experiments were performed in which the effects of two β-blockers, tertatolol [dl-(hydroxy-2’-t-butyl-amino-3’-propyloxy)-8-thiochroman hydrochloride] and propranolol, on mean arterial pressure (MAP), heart rate (HR), and renal function were studied in the conscious sodium-replete dog. In all experiments renal function was evaluated from the effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) assessed respectively by measurement of p-aminohippurate and creatinine clearances. These parameters were measured during two 30-min control periods, after which two further measurements were performed over a similar time period, after intravenous administration of either propranolol (0.5 mg·kg^-1; n = 8) or tertatolol (0.05 mg·kg^-1; n = 8), these two doses being of equivalent β-adrenoceptor antagonist activity. Administration of propranolol and tertatolol did not change MAP but induced a significant and comparable decrease in HR. After propranolol a significant decrease in ERPF was observed, without any change in GFR or sodium excretion. In contrast, administration of tertatolol resulted in no modification of ERPF, a slight but significant increase in GFR, and a significant increase in sodium and potassium excretion. These results suggest that tertatolol and propranolol though acting similarly on systemic parameters have different effects on renal hemodynamics in the conscious dog.

Long-Term Experience with Tertatolol in Hypertension

“…Indeed, a renal function impair ment is generally observed when this treatment is intro duced and continues with long-term administration [8,9]. In contrast, this 1-year study confirms the beneficial effect of tertatolol on renal function previously observed in experimental [17,18] and short-term studies [19][20][21], Particularly, in keeping with what was reported by Ardaillou [20], the decrease in plasma creatinine level is greater the greater the initial level is. and reaches almost 20% in the upper-range subgroup.…”

“…One of the reasons supposed to account for this phenomenon is the lack of any important salt and water retention during ß-blocker treatment, as shown by the stability of the patient's body weight during this study. The effects of tertatolol on renal function [17][18][19][20][21][22] further support this explanation.…”

Effects of Tertatolol in Hypertensive Patients with Chronic Renal Failure

“…It also has some pecu liar properties regarding renal hemodynamics. Laubie et al [29] and Walker et al [30] have shown that renal plasma flow measured by paraaminohippurate clearance and GFR measured by inulin clearance are unaffected by intravenous administration of tertatolol [29,30]. In spontaneously hypertensive rats, Struyker-Boudier et al [31] have shown that tertatolol induces a reduction of renal vascular resistance.…”

Hemodynamic Effects of Beta-Blockade in Hypertension

“…a redistribution towards the hepatosplanchnic circulation has also been shown [19], Finally, the best example is given by the (3-blocking drug tertatolol: while cardiac output is reduced and total peripheral resistance elevated, a striking vasodilation in the kidney is ob served at the same time. Following acute administration, the preserved renal plasma flow observed with tertatolol appears to be the consequence of a lack of vasoconstric tion within the kidney; this takes place in the context of a systemic vasoconstriction [20][21][22]. Following chronic administration, the preserved or increased renal plasma flow appears to be the consequence of renal vasodilation, this takes place in the context of the long-term adapta tion of vascular resistance [20][21][22][23].…”

“…Following acute administration, the preserved renal plasma flow observed with tertatolol appears to be the consequence of a lack of vasoconstric tion within the kidney; this takes place in the context of a systemic vasoconstriction [20][21][22]. Following chronic administration, the preserved or increased renal plasma flow appears to be the consequence of renal vasodilation, this takes place in the context of the long-term adapta tion of vascular resistance [20][21][22][23]. Furthermore, the vasodilation is more effective in the presence of an ini tial background of renal vasoconstriction, as can be observed in sustained essential hypertension, thus result ing in an absolute increase in renal plasma flow.…”