Involvement of Renin–Angiotensin System Inhibition, the Potential Risk of Danshen in the Treatment of Pregnancy‐Induced Hypertension

Hypertension is the most common medical problemof pregnancy and contributes significantly tomaternal and perinatal morbidity and mortality(Vellore, 2011). Although physicians have recognizedpregnancy-induced hypertension (PIH) for years, itspathogenesis still remains unclear. Considering thereare limited data from large well-designed random-ized trials strongly recommending the use of onedrug is superior to another in PIH, traditional Chi-nese medicine is gradually appealing to physicians’interest in China.Danshen, the dried root of Salvia miltiorrhizae (Fam.Labiatae), is an extremely popular drug in China, whichhas been used alone or in combination with other herbalingredients for hundreds of years in the treatment ofcoronary heart diseases, myocardial infarction, andhypertension (Tang and Eisenbrand, 1992) and also suc-cessfully used as a complementary therapy for PIH(Wang and Zhao, 2003).Modern pharmacology discovered that the anti-hypertensive effect of Danshen is mediated throughthe inhibition of angiotensin-converting enzyme, anessential regulatory enzyme of the renin–angiotensinsystem (RAS) (Kang et al., 2002, 2003; Gao et al.,2004; Jiang et al., 2005). Lithospermic acid B (Kanget al., 2003) and salvianolic acid B (Gao et al., 2004)are two main components of Danshen responsible forits anti-hypertensive effect. Some researchers alsodemonstrated that Danshen is an effective inhibitor ofangiotensin II, which has been shown to suppress an-giotensin II-induced myocardial hypertrophy in neona-tal rats (Haber et al., 1994; Ouyang et al., 2002; Hanet al., 2002).Angiotensin-converting enzyme inhibitors (ACEIs)are a group of compounds used in the management ofhypertension (Lonn et al., 1994). In vitro studies haveshown that ACEIs could cross the sheep (Stevensonet al., 1995) and human (Reisenberger et al., 1996)placentae. Evidence from animal studies furthershowed that administration of ACEIs during preg-nancy is associated with fetal toxicity and an increaserate in stillbirths (Broughton Pipkin et al., 1990;Harewood et al., 1994). Moreover, the use of ACEIsin humans during late pregnancy has been proved tobe associated with a characteristic fetopathy includingrenal dysplasia, oligohydramnios, hypocalvaria, limbcontractures, pulmonary hypoplasia, and intrauterinegrowth restriction (Guignardet al., 1991; Rosa et al.,1989; Barr and Cohen, 1991; Barr, 1994). The use ofangiotensin II receptor antagonists, also known as an-giotensin receptor blockers (ARBs), during the secondand third trimesters of pregnancy has also been associ-ated with similar fetotoxicity (Schaefer, 2003; Alwanet al., 2005).Although there is a general controversy about theteratogenicity of ACEIs (ARBs) in the first trimester,fetal adverse effects in the second and third trimestersare well documented (Quan, 2006). More and moreinvestigators recommend that maternal treatment withACEIs and ARBs should be avoided during the secondand third trimesters of pregnancy, and those womenwho become pregnant while taking one of thesemedications should be switched to an effective anti-hypertensive drug of a different class that does notdamage RAS function as soon as the pregnancy isrecognized.We do not doubt that Danshen has great signifi-cance in its clinical application; however, with thedevelopment of the research, the huge risks for preg-nancy caused by its chemical compositions that is con-traindicated in the second and third trimesters ofpregnancy must be paid more attention, and furtherstudies are needed to verify the safety of Danshenfor PIH.Conflict of Interest